annual review of chronopharmacology
TRANSCRIPT
ANNUAL REVIEW OF CHRONOPHARMACOLOGY
Vo lume 1
BIOLOGICAL RHYTHMS AND MEDICATIONS P r o c e e d i n g s of t h e F i r s t M o n t r e u x C o n f e r e n c e of C h r o n o p h a r m a c o l o g y , M o n t r e u x , 2 6 - 3 0 M a r c h 1 9 8 4
E d i t o r s :
A. R E I N B E R G F o n d a t i o n A . d e R o t h s c h i l d , P a r i s , F r a n c e
M . S M O L E N S K Y U n i v e r s i t y of T e x a s , H o u s t o n , U . S . A .
G. L A B R E C Q U E U n i v e r s i t e d e L a v a l , Q u e b e c , C a n a d a
P E R G A M O N P R E S S
O X F O R D • N E W Y O R K T O R O N T O • S Y D N E Y • PARIS • F R A N K F U R T
C O N T E N T S
Section 1 — Neurobiology C h a i r m e n : A . W I R Z - J U S T I C E (Base l , S w i t z e r l a n d )
W . R I E T V E L D ( L e i d en , N e t h e r l a n d )
T h e e f fec t of p a r t i a l l e s i o n s of t h e h y p o t h a l a m i c s u p r a c h i a s m a t i c n u c l e u s o n t h e c i r c a d i a n c o n t r o l of b e h a v i o u r
W . J . R I E T V E L D
I n v i v o v o l t a m m e t r y : m o n i t o r i n g d r u g i n d u c e d c h a n g e s i n 5 H T at t h e s u p r a c h i a s m a t i c n u c l e u s l e v e l
K. F . M A R T I N a n d C. A . M A R S D E N
Ef f ec t o f p r o l o n g e d a d m i n i s t r a t i o n of c l o m i p r a m i n e o n 24 -hou r V a r i a t i o n i n 5 H T m e t a b o l i s m i n t h e ra t b r a i n
K. F . M A R T I N a n d P. H . R E D F E R N
C h r o n o p h a r m a c o l o g i c a l a l t e r a t i o n s i n p e n t o b a r b i t a l i n d u c e d h y p n o s i s a n d b o d y t e m p e r a t u r e p r o d u c e d b y d r u g s i n f l u e n c i n g b r a i n m o n o a m i n e s
S. G . S P E C I A L E a n d A . H . F R I E D M A N
C i r c a d i a n d y s r h y t h m i a s i n t h e E E G of c h i l d r e n w i t h c l o n a z e p a m t r e a t m e n t
B. A R B O G A S T , M . H A L L E K , H . A R B O G A S T , T. HELLBRÜGGE a n d R. S C H M I D
T e m p o r a l a n d s e x r e l a t e d v a r i a t i o n s of l o r a z e p a m k i n e t i c s B. B R U G U E R O L L E , G . B O U V E N O T a n d R. B A R T O L I N
Ef fec ts of d i f f e rent t r e a t m e n t s o n t h e c i r c a d i a n r h y t h m of p l a s m a p r o l a c t i n i n P a r k i n s o n ' s d i s e a s e
E . F E R R A R I , G . M I C I E L I , P. A . B O S S O L O , E . M A R T I G N O N I , L. M A G N A N I a n d G . N A P P I
x i i i
xiv Contents
C i r c a d i a n r h y t h m s i n t h e w a k i n g E E G 29 A . G U N D E L
C i r c a d i a n p a t t e r n s o f p l a s m a 3 - m e t h o x y - 4 -h y d r o x y p h e n y l g l y c o l ( M H P G ) i n n o r m a l a n d d e p r e s s e d s u b j e c t s 33
A . H A L A R I S
C i r c a d i a n d y s r h y t h m i a i n t h e b e h a v i o r of e p i l e p t i c c h i l d r e n w i t h c l o n a z e p a m and/o r p h e n o b a r b i t a l t r e a t m e n t 37
M . H A L L E K , B . A R B O G A S T , T . HELLBRÜGGE, R. S C H M I D , H . A R B O G A S T a n d B . K L E I S E R
Q u a n t i t a t i v e c h r o n o p h a r m a c o d y n a m i c e n d p o i n t i n h e a l t h a n d s c h i z o p h r e n i a : t i m i n g of p l a s m a d e h y d r o e p i a n d r o s t e r o n e ( D H E A ) v e r s u s D H E A - s u l f a t e 41
B . K L E I S E R , F . H A L B E R G , G . C O R N E L I S S E N a n d C . V A N V A L K E N B U R G
E f f e c t of b e n z t r o p i n e o n p l a s m a h a l o p e r i d o l c h r o n o p h a r m a c o l o g y a n d b l o o d c h o l i n e l e v e l s i n m a n 45
R. S. N A T H A N , J . M . P E R E L , I. H A N I N , U . K O P P , T . M C C A R T H Y a n d R. S T I L L E R
A c o m p a r i s o n o f t h r e e - t i m e - d a i l y a n d S ing l e d o s e r e g i m e of h a l o p e r i d o l 49
R. L U N D a n d E . RÜTHER
G a m m a - a m i n o b u t y r i c a c i d a n d t h e n e u r a l b a s i s of c i r c a d i a n t i m e k e e p i n g : i m p l i c a t i o n s for p a t h o p h y s i o l o g y a n d p s y c h o p h a r m a c o t h e r a p y o f c i r c a d i a n b a s e d d i s o r d e r s 53
D. B O R S O O K , M . C . M O O R E - E D E , T . H E D B E R G , G . R I C H A R D S O N a n d M . J . W . B R E N N A N
Section 2 — Antihistamines & Bronchodilators
C h a i r m e n : M . S M O L E N S K Y ( H o u s t o n , T e x a s , U .S .A . ) A . R E I N B E R G (Par i s , F r a n c e )
A n t i h i s t a m i n e a n d o t h e r e f f ec ts o f 5 m g m e q u i t a z i n e v a r y b e t w e e n m o r n i n g a n d e v e n i n g a c u t e a d m i n i s t r a t i o n 57
A . R E I N B E R G , F . L E V I , J . P. F O U R T I L L A N , C. P E I F F E R , A . B I C A K O V A - R O C H E R a n d A . N I C O L A I
Contents xv
B i o l o g i e t i m e r e l a t e d c h a n g e s i n a n t i - h i s t a m i n e a n d o t h e r e f f e c t s of c h r o n i c a d m i n i s t r a t i o n of m e q u i t a z i n e i n h e a l t h y a d u l t s 61
A . R E I N B E R G , F . L E V I , A . B I C A K O V A - R O C H E R , J . P . B L U M , M . M . O U E C H N I a n d A . N I C O L A I
M u l t i c e n t r i c c h r o n o t h e r a p e u t i c s t u d y o f m e q u i t a z i n e i n p a t i e n t s w i t h a l l e r g i c r h i n i t i s 65
P. G E R V A I S
C o m p a r i s o n o f n o c t u r n a l a n d d i u r n a l t h e o p h y l l i n e l e v e l s a t s t e a d y - s t a t e 69
S. S A M A A N , R. F O X , S. B U K A N T Z a n d R. L O C K E Y
C h r o n o p h a r m a c o l o g y o f t h e o p h y l l i n e , w i t h s p e c i a l r e f e r e n c e to a g e 73
J . H . G . J O N K M A N a n d M . H . S M O L E N S K Y
C i r c a d i a n r h y t h m s i n s t e a d y - s t a t e t h e o p h y l l i n e p h a r m a e o k i n e t i c s i n c h i l d r e n 77
W . G . K R A M E R , P. H . S C O T T , M . H . S M O L E N S K Y , R. H A R R I S T , P. H I A T T , J . B A E N Z I G E R , B . K L A N K a n d H . E I G E N
C i r c a d i a n Variat ion i n t h e o p h y l l i n e a b s o r p t i o n 81 M . St . P E I R R E , S. L E E D E R , M . S P I N O , A . I S L E S a n d S. M a c L E O D
V a r i a t i o n i n t h e o p h y l l i n e l e v e l s f o l l o w i n g m o r n i n g o r e v e n i n g a d m i n i s t r a t i o n 85
W . R. P R I M R O S E
T h e ef fect o f s u s t a i n e d - r e l e a s e t h e o p h y l l i n e o n t h e c i r c a d i a n V a r i a t i o n o f p u l m o n a r y f u n e t i o n i n p e d i a t r i c a s t h m a t i c p a t i e n t s 89
P. S C O T T , R. H A R R I S T , M . S M O L E N S K Y , W . K R A M E R , P. H I A T T , J . B A E N Z I G E R , B . K L A N K a n d H . E I G E N
A c h r o n o p h a r m a e o k i n e t i e m o d e l for c o n t r o l l e d - r e l e a s e f o r m u l a t i o n s 93
A . S T R A U G H N , M . M E Y E R , A . G O L U B a n d M . G O N Z A L E Z
C h r o n o p h a r m a c o k i n e t i c s o f ca f f e ine i n h e a l t h y v o l u n t e e r s 97 M . L E V Y , L . G R A N I T a n d E . Z Y L B E R - K A T Z
S l o w r e l e a s e t e r b u t a l i n e i n n o c t u r n a l b r o n c h i a l o b s t r u e t i o n : r e l a t i on of t e r b u t a l i n e d o s a g e a n d b l o o d l e v e l s w i t h c i r c a d i a n c h a n g e s i n p e a k f l o w v a l u e s 101
D. S. P O S T M A , G . H . K O E T E R , H . M E U R S a n d J . J . K E Y Z E R
xv i Contents
N o c t u r n a l b r o n c h i a l o b s t r u c t i o n : i n f l u e n c e o f s l o w r e l e a s e t e r b u t a l i n e o n c i r c a d i a n r h y t h m of s p i r o m e t r y , h i s t a m i n e a n d c a t e c h o l a m i n e s 105
D . S. P O S T M A , G . H . K O E T E R , H . M E U R S a n d J . J . K E Y Z E R
Section 3 — Anticancerous Medications & Cancer C h a i r m e n : L . E . S C H E V I N G ( L i t t l e R o c k , A r k a n s a s ,
U .S .A . ) E . H A U S ( S a i n t - P a u l , M i n n . , U .S .A . )
M e a l s c h e d u l i n g , f a s t i n g , c e l l u l a r r h y t h m s a n d c h r o n o p t h e r a p y of C a n c e r 109
L . A . S C H E V I N G , T . H . T S A I , L . E . S C H E V I N G a n d J . E . P A U L Y
C i r c a d i a n V a r i a t i o n i n s e r u m c o n c e n t r a t i o n o f c a r c i n o e m b r y o n i c a n t i g e n ( C E A ) i s a l t e r e d i n Cance r p a t i e n t s 111
C . F O C A N , V . C A S T R O N O V O , J . C O L L E T T E , D. F O C A N -H E N R A R D , M . H . F R E R E , S. L E H U N G , Y . T O U I T O U a n d P. F R A N C H I M O N T
C i r c a d i a n r h y t h m i n c i s p l a t i n b i n d i n g o n p l a s m a p r o t e i n s 115 B . H E C Q U E T , J . M E Y N A D I E R , J . B O N N E T E R R E a n d L. A D E N I S
C i r c a d i a n c h r o n o p h a r m a c o k i n e t i c s a n d c h r o n o t o x i c o l o g y of d o x o r u b i c i n a n d c i s p l a t i n i n h u m a n b e i n g s w i t h C a n c e r 119
W . J . M . H R U S H E S K Y
P r o t e i n s y n t h e s i s i n h u m a n t u m o r c e l l p o p u l a t i o n s — g o v e r n e d b y p e r i o d i c a l l y t r a n s f e r r e d S i g n a l s 123
T . L E D E R E R , A . L E H M E R a n d K. Z Ä N K E R
C h r o n o p h a r m a c o l o g y : a c r i t i c a l s t a g e i n t h e d e v e l o p m e n t of a n t i c a n c e r d r u g s ? T H P a d r i a m y c i n as a n e x a m p l e 127
F . L E V I , J . P. B L U M , G . L E M A I G R E , M . M E C H K O U R I , A . R O U L O N , A . R E I N B E R G a n d G . M A T H E
C i r c a d i a n r h y t h m s i n 6 c i r c u l a t i n g l y m p h o c y t e S u b t y p e s i n h e a l t h y m e n : a 100- f o ld V a r i a t i o n m a y b e P h y s i o l o g i e 131
F . L E V I , C . C A N O N , J . P. B L U M , J . L. M I S S E T , M . M E C H K O U R I , M . B E N N A C E U R a n d G . M A T H E
M u l t i f r e q u e n c y c h r o n o t h e r a p y w i t h c i r c a s e p t a n a n d e v e n t u a l l y c i r c a n n u a l o p t i m i z a t i o n m a y f o l l o w ea r l y c i r c a d i a n - s i n u s o i d a l p u m p - i m p l e m e n t e d i n f u s i o n s of c y c l o s p o r i n e 133
T. L I U , M . C A V A L L I N I , F . H A L B E R G , G . C O R N E L I S S E N , J . F I E L D a n d D . E . R. S U T H E R L A N D
Contents x v i i
C h r o n o b i o l o g y o f u r a t e e x c r e t i o n a f t e r c y t o s t a t i c t r e a t m e n t 137 M . H . R O B I N S O N , M . S. K N A P P a n d R. P O W N A L L
P l a s m a c a r c i n o e m b r y o n i c a n t i g e n r h y t h m i n p a t i e n t s w i t h o v a r i a n c a n c e r : e f f ec ts o f c h e m o t h e r a p y 141
Y . T O U I T O U , W . H R U S H E S K Y , C . F O C A N , A . A U Z E B Y a n d A . B O G D A N
E f f e c t of c o r t i c o s t e r o i d s a n d m e l a t o n i n o n t h e c i r a d i a n r h y t h m o f m e t h o t r e x a t e t o x i c i t y i n t h e r a t 145
J . E N G L I S H , G . W . A H E R N E a n d J . A R E N D T
T h e e f fect o f c i r c a d i a n r h y t h m o n i m m u n e f u n c t i o n a n d s p l e n i c l y m p h o c y t e s u b s e t r a t i o s i n m i c e 149
G . F E R N A N D E S , N . T A L A L a n d J . D E H Ä V E N
Section 4 — Statistics, Methods and Instrumentation (Including Pumps)
C h a i r m e n : J . D e P R I N S (Brüssels, B e l g i u m ) W . H R U S H E S K Y ( M i n n e a p o l i s , M i n n . . U .S .A . )
S e r i a l s e c t i o n w i t h f l e x i b l e p e r i o d c o r r e c t i o n a n d a n a p p l i c a t i o n i n l o n g t e r m E E G a n a l y s i s 153
B . A R B O G A S T a n d T H . HELLBRÜGGE
A u t o m a t i c d e t e c t i o n o f m u l t i p l e o u t l i e r s i n P h y s i o l o g i e t i m e s e r i e s : n o t a b l y t e m p e r a t u r e 157
G . C O R N E L I S S E N
T h e development of n e w Statist ical methods for e v e n t d e t e c t i o n i n t ime s e r i e s 161
R. P O W N A L L , K. G O R D O N , M . S. K N A P P a n d A . F. M . S M I T H
C o r t i s o l m a r k e r r h y t h m o m e t r y i n p e d i a t r i c s a n d c l i n i c a l p h a r m a c o l o g y 165
E . H A E N , F . H A L B E R G a n d G . C O R N E L I S S E N
C i r c a d i a n a n d u l t r a d i a n r h y t h m p e r i o d a l t e r a t i o n s i n a p p a r e n t l y h e a l t h y s u b j e c t s w i t h a n d w i t h o u t p l a c e b o 169
A . B I C A K O V A - R O C H E R , A . G O R C E I X a n d A . N I C O L A I
A c h r o n o p h a r m a c o l o g i c a l m o d e l of p s y c h o t r o p i c d r u g a c t i o n a n d i ts p r a c t i c a l i n c i d e n c e o n p h a s e s I a n d II m e t h o d o l o g y 173
J . D O U C H A M P S , J . L . G U I S S E T , J . P. B I N O N , J . M . B A R R E , B . G H I S T E a n d P. T U B E L L O
A n e x p e r i m e n t a l d e s i g n for e v a l u a t i n g t r e a t m e n t e f f ec ts a n d c i r c a d i a n r h y t h m i n r e s p i r a t o r y f u n c t i o n 177
R. B. H A R R I S T , M . H . S M O L E N S K Y a n d P. H . S C O T T
xv i i i Contents
R h y t h m o m e t r y a n a l y s i s o n p e r s o n a l C o m p u t e r s for a p p l i c a t i o n s t o c h r o n o p h a r m a c o l o g y s t u d i e s 181
B. P. H S I
M i c r o p r o c e s s o r - b a s e d a m b u l a t o r y t e m p e r a t u r e a n d a c t i v i t y r e c o r d e r 183
J . N O U G U I E R - S O U L E a n d J . N O U G U I E R
D i u r n a l Variation i n g l u c o s e l e v e l s c a n i m p e d e Single rate c o n t i n u o u s i n t r a v e n o u s i n s u l i n t h e r a p y 185
E . P. C H U T E , T . D . R O H D E , W . M . R U P P , F. J . G O L D E N B E R G , W . J . M . H R U S H E S K Y a n d H . B U C H W A L D
A n e w t e c h n i q u e t o s t u d y t h e e f fect of d y n a m i c a d m i n i s t r a t i o n of b i o c h e m i c a l a g e n t s i n v i t r o a n d i n v i v o 189
M . L . G R U E N B E R G a n d J . J . P E L U S O
I m p l a n t a b l e a n d e x t r a c o r p o r e a l p r o g r a m m a b l e d r u g d e l i v e r y S y s t e m s : w h a t t o p r o g r a m 193
B . J . K E N N E D Y , D . C O V E L L a n d W . J . M . H R U S H E S K Y
A p h a s e I t r i a l o f a n i m p l a n t e d l i t h i u m b a t t e r y - p o w e r e d d r u g a d m i n i s t r a t i o n d e v i c e S y s t e m ( D A D S , M e d t r o n i c , inc.) for c o n t i n u o u s d o x o r u b i c i n i n f u s i o n (CDI) 197
N . J . V O G E L Z A N G
M i c r o c o m p u t e r - r e l a t e d m o d u l e s for e x p e r i m e n t a l s t a n d a r d i z a t i o n a n d t e m p e r a t u r e - a c t i v i t y - r h y t h m o m e t r y i n p h a r m a c o l o g y , t o x i c o l o g y a n d b i o l o g y 201
E . H A L B E R G , B . B R O C K W A Y , D . O S G O O D , W . N E L S O N , J . H A L B E R G , S. S A N C H E Z D e L a P E N A a n d F . H A L B E R G
Section 5 — Endocrinology & Reproduction
C h a i r m e n : I. A S S E N M A C H E R ( M o n t p e l l i e r , F r a n c e ) Y . T O U I T O U (Par i s , F r a n c e )
R e g u l a t i o n a n d d r u g e f fect o n t h e l i g h t - d e p e n d e n t c i r c a d i a n p r o l a c t i n r h y t h m s i n e s t r o g e n p r i m e d f e m a l e r a t s 205
R. D O R O W , H . W A C H T E L , K. J . R E T T I G , S. H A S A N a n d R. H O R O W S K I
P i n e a l r h y t h m s : m o d i f i c a t i o n b y d r u g s a n d l i g h t 207 R. J . R E I T E R
Contents x ix
T h e u s e of t w o d i f f e r en t l i g h t i n g r e g i m e n s a l l o w s t h e d i s s o c i a t i o n of t h e m e c h a n i s m s r e s p o n s i b l e for t h e a c t i o n of m e l a t o n i n o n e s t r o u s c y c l e s a n d t h o s e p r o v o k i n g t h e p r o e s t r o u s s u r g e o f g o n a d o t r o p i n s 211
R. W . R I V E S T , U . L A N G , M . L . ÄUßERT , M . F . N A W R A T I L , A . S C H E R R E R a n d P. C . S I Z O N E N K O
A p p a r e n t a b s e n c e of i n f l u e n c e of m e l a t o n i n o n t h e c i r c a d i a n r h y t h m i n c e l l d i v i s i o n 2 1 5
N . H . R U B I N , R. J . R E I T E R a n d J . A . H O K A N S O N
C i r c a d i a n r h y t h m i n c A M P c o n t e n t a n d i n t h e a c t i v i t i e s of b a s a l a d e n y l a t e c y c l a s e a n d P h o s p h o d i e s t e r a s e i n r a t h e a r t v e n t n c l e s 219
P . - H . L A N G , H . B I S S I N G E R a n d B . L E M M E R
C i r c a n n u a l p e a k - s h i f t i n c i r c a d i a n r h y t h m i n b a s a l c A M P c o n t e n t i n ra t h e a r t v e n t r i c l e s 223
B. L E M M E R , P . - H . L A N G a n d H . B I S S I N G E R
In t e r f e r ence w i t h c i r c a d i a n r h y t h m s o f h e m o p o i e s i s b y a s y n t h e t i c h e m o r e g u l a t o r y p e p t i d e 227
0 . D. L A E R U M a n d W . R. P A U K O V I T S
S e a s o n a l v a r i a t i o n s i n t h e h u m o r a l i m m u n e r e s p o n s e i n m i c e f o l l o w i n g a d m i n i s t r a t i o n of t h y m i c h o r m o n e s 231
M . D O U C E T - J A B O E U F , A . P E L E G R I N , M . C . C O T , J . G U I L L E M A I N a n d M . B A S T I D E
C i r c a d i a n d e p e n d e n t e f fect o f e p i d e r m a l g r o w t h fac tor , i n s u l i n a n d g l u c a g o n o n h e p a t i c p y r u v a t e k i n a s e a n d m a l i c e n z y m e of m i c e 2 3 5
R. J . F E U E R S , R. R. D E L O N G C H A M P , L . A . S C H E V I N G , T. H . T S A I , D . A . C A S C I A N O , J . E . P A U L Y a n d L. E . S C H E V I N G
R e s p o n s e s of n y m p h s of t h e l a r g e m i l k w e e d b u g a n d p u p a e of the y e l l o w m e a l w o r m t o t h r e e C o m p o u n d s a f f e c t i n g i n sec t g r o w t h 239
R. E . R E D F E R N , D . K. H A Y E S , J . D . W A R T H E N , J R . , A . B. D e M I L O a n d T . P. M c G O V E R N
L o s s of circadian r h y t h m i c i t y i n p l a s m a t e s t o s t e r o n e l e v e l s i n adult m e n w i t h C u s h i n g ' s Syndrome or under long-term t r e a t m e n t w i t h glucocort icoids 243
A . A N G E L I , G . B E L L O T T I , C . D E M I C H E L I , G . G A T T I , R. C A V A L L O , V . G A L L O a n d F . A G R I M O N T I
XX Contents
C i r c a d i a n p a t t e r n s o f c o r t i s o l a n d a l d o s t e r o n e i n p l a s m a , u r i n e a n d p e r i t o n e a l f l u i d of c h r o n i c u r e m i c p a t i e n t s u n d e r c o n t i n u o u s a m b u l a t o r y p e r i t o n e a l d i a l y s i s 247
F . A G R I M O N T I , G . T R I O L O , M . S A L O M O N E , D. B I S B O C C I , G . P I N N A , C . M A R I N O N E a n d A . A N G E L I
C i r c a d i a n - e f f e c t of s o m a t o s t a t i n , g l u c a g o n , i n s u l i n , e p i d e r m a l g r o w t h factor , p e n t a g a s t r i n a n d A C T H 1—17 o n c e l l p r o l i f e r a t i o n i n m i c e 251
L . E . S C H E V I N G , T . H . T S A I , L . A . S C H E V I N G a n d J . E . P A U L Y
Section 6 — Metabolism & Nutrition C h a i r m e n : H . N A K A G A W A ( O s a k a , J a p a n )
A . A N G E L I ( To r ino , I ta ly )
C i r c a d i a n r h y t h m s of f o o d i n t a k e a n d p r o t e i n s e l e c t i o n i n y o u n g a n d o l d r a t s 255
P. D . L E A T H W O O D a n d L . A R I M A N A N A
C h r o n o p h a r m a c o l o g i c a l s t u d i e s o n c e n t r a l r e g u l a t i o n of b l o o d s u g a r h o m e o s t a s i s 259
H . N A K A G A W A , K. N A G A I , T . M O R I a n d H . Y A M A M O T O
R o l e of f e e d i n g s c h e d u l e a n d p h a r m a c o k i n e t i c s i n c h r o n o p h a r m a c o l o g y of d r u g s a c t i n g o n t h e c e n t r a l n e r v o u s S y s t e m 263
S. N A K A N O , K. N A G A I a n d N . O G A W A
C i r c a d i a n a n d c i r c a h e m i d i a n v a r i a t i o n s of t h e a c t i v e c a l c i u m a b s o r p t i o n : e f f ec ts of d i e t r y a n d e n v i r o n m e n t a l c h a n g e s 267
D . P A N S U , C . R O C H E , C . B E L L A T O N , M . M E C H K O U R I a n d T H . T E U V E N Y
C o s i n o r a n d s p e c t r a l a n a l y s i s o f c i r c a n n u a l r h y t h m s of m u c o u s , a c i d a n d p e p t i c g a s t r i c s e c r e t i o n s i n c a t s 271
D. P A N S U , M . V A G N E , M . C O L L I N E T , A . D E S V I G N E , A . R E I N B E R G a n d M . M E C H K O U R I
C i r c a d i a n v a r i a t i o n s of p lasma histamine a n d c i r c u l a t i n g leucocyte Subtypes i n m a g n e s i u m d e p r i v e d rats
M . B E N N A C E U R , O. F E R M E N T , B . L E B E L a n d 275 F . G A U D I N - H A R D I N G
U l t r a d i a n , c i r c a d i a n a n d c i r c a n n u a l r h y t h m s of b l o o d g l u c o s e a n d i n j e c t e d i n s u l i n d o c u m e n t e d i n s e l f - c o n t r o l l e d d i a b e t i c s 279
M . K O L L O P , A . B I C A K O V A - R O C H E R , P. D R O U I N , L . M E J E A N a n d G . D E B R Y
Contents xx i
C o r r e l a t i o n b e t w e e n c i r c a d i a n - s t a g e d e p e n d e n t v a r i a t i o n s o f o r a l g l u c o s e t o l e r a n c e t e s t a n d a l i m e n t a r y p a t t e r n s i n y o u n g s u b j e c t s w i t h d i a b e t i c f a m i l y h i s t o r y 283
P. M A R R I N O , G . R A V A G L I A , M . C A P E L L I , S. E . C O G L I A N D R O , F . A G R I M O N T I , D . F O R N A R O a n d A . L O D I
C i r c a d i a n a n d u l t r a d i a n r h y t h m s i n a c u t e r e s p i r a t o r y f a i l u r e : e f f ec ts o f b o t h c o n t i n u o u s e n t e r a l f e e d i n g a n d r a n i t i d i n e (H2 r e c e p t o r b l o c k e r ) i n f u s i o n at c o n s t a n t r a t e 287
J . P. A C C A R Y , D . R I G A U D , J . C H A S T R E , F . C A N T O W I T Z , C . G I B E R T a n d S. B O N F I L S
P o s t o p e r a t i v e e n t e r a l f e e d i n g p a t t e r n s a n d d i u r n a l t e m p e r a t u r e r h y t h m s 291
I. T . C A M P B E L L , R. P. M O R T O N a n d P. M . S T E L L
C l i n i c a l s t u d y of c y c l i c ( noc tu rna l ) t o t a l p a r e n t e r a l a n d c o n t i n u o u s e n t e r a l n u t r i t i o n ( i n c l u d i n g l i p i d s ) o n c i r c a d i a n r h y t h m s i n s e r u m l i p i d s , l i p o p r o t e i n s , a p o l i p o p r o t e i n s a n d g l u c o s e 295
J . F A B R E , O. G U I L L A R D , D . R E I S S a n d C . M A T U C H A N S K Y
O b s e r v a t i o n s o n t h e p h a r m a c o k i n e t i c s o f e t h a n o l 297 D . L A K A T U A , T . S. L E S A R , D. E . Z A S K E , W . A . W A R G I N a n d E . H A U S
C i r c a d i a n r h y t h m s of i n s u l i n e a n d H G H s e c r e t i o n i n h e a l t h y a n d d i a b e t i c c h i l d r e n 301
A . M R O Z I K I E W I C Z a n d D . K I E L C Z E W S K A - M R O Z I K I E W I C Z
I n c r e a s e d s t o m a c h s i z e a n d m o r t a l i t y o b s e r v e d i n a d l i b i t u m f e d C D 2 F a a d u l t male m i c e i n j e c t e d w i t h i n s u l i n , g l u c a g o n , e p i d e r m a l g r o w t h f ac to r , s a l i v a , or s y m p a t h o m e t i c submandibular g land St imulat ion 305
L. A . S C H E V I N G , T . H . T S A I , L. E . S C H E V I N G a n d J . E . P A U L Y
Section 7 — Cardiovascular and Antiinflammatory Agents
C h a i r m e n : B . L E M M E R ( F r a n k f u r t / M . , W e s t G e r m a n y G . L A B R E C Q U E ( Q u e b e c , C a n a d a )
B i o l o g i c a l r h y t h m stüdies o n t h e h y p o t e n s i v e a c t i o n of P r o s t a g l a n d i n E 2 a n d a r a c h i d o n i c a c i d i n t h e r a t 309
F. D O R E , G . L A B R E C Q U E , C . D ' A U T E U I L a n d P. M . B E L A N G E R
xx i i Contents
C h r o n o p h a r m a c o l o g i c a l s t u d i e s o f d i u r e t i c s i n h y p e r t e n s i v e r a t s 313
F. D O R E , C . D ' A U T E U I L , G . L A B R E C Q U E a n d P. M . B E L A N G E R
C h r o n o p h a r m a c o k i n e t i c s o f t h e b e t a - a d r e n o c e p t o r - b l o c k i n g d r u g s P r o p r a n o l o l , m e t o p r o l o l , S o t a l o l a n d a t e n o l o l i n p l a s m a a n d o r g a n s a f ter Single a n d m u l t i p l e d o s i n g i n t h e ra t 317
B . L E M M E R , H . W I N K L E R , M . F I N K a n d T . O H M
C i r c a d i a n - s t a g e - d e p e n d e n c y i n a n t a g o n i s t b i n d i n g of 3 H - d i h y d r o a l p r e n o l o l t o r a t h e a r t v e n t r i c u l a r m e m b r a n e s 321
B . L E M M E R a n d P . - H . L A N G
T h e S i n e - O - G r a p h p u l s e m o n i t o r : a p o t e n t i a l q u a n t i f i e r of c a r d i o v a s c u l a r W e l l n e s s 325
W . J . M . H R U S H E S K Y
C i r c a t r i g i n t a n a n d c i r c a n n u a l a n g i n a c r i s e s a n d i s o s o r b i d e d i n i t r a t e c o m p l i a n c e r h y t h m s 329
R. W . M O R R I S
C i r c a d i a n r h y t h m s t u d i e s o n B C G - i n d u c e d m i g r a t i o n of P M N i n n o r m a l a n d a d r e n a l e c t o m i z e d m i c e 333
J . P. B U R E A U , L . G A R R E L L Y , M . C O U P E a n d G . L A B R E C Q U E
C i r c a n n u a l r h y t h m s of P M N m i g r a t i o n i n d u c e d b y B C G i n i n t a c t m i c e 337
J . P. B U R E A U , M . C O U P E , L . G A R R E L L Y a n d G L A B R E C Q U E
C h r o n o p h a r m a c o k i n e t i c s t u d y o f i n d o m e t h a c i n 341 G . C U I S I N A U D , P. G U I S S O U a n d J . S A S S A R D
C h r o n o t h e r a p y of o s t e o a r t h r i t i c p a t i e n t s : o p t i m i z a t i o n of i n d o m e t h a c i n s u s t a i n e d r e l e a s e (ISR) 345
F . L E V I , C . L e L O U A R N a n d A . R E I N B E R G
C h r o n o b i o l o g i c a l c o n s i d e r a t i o n s of a s p i r i n a n d i n d o m e t h a c i n 349 L. P Ö L L M A N N
K e t o p r o f e n c h r o n o k i n e t i c s i n h u m a n v o l u n t e e r s 353 P. Q U E N E A U , M . O L L A G N I E R , H . D E C O U S U S , Y . C H E R R A H a n d B . P E R P O I N T
P r e l i m i n a r y o b s e r v a t i o n s f r o m a d o u b l e b l i n d c r o s s o v e r s t u d y t o e v a l u a t e t h e e f f i cacy of f l u r b i p r o f e n g i v e n at d i f f e r en t t i m e s of d a y i n t h e t r e a t m e n t o f r h e u m a t o i d a r t h r i t i s 357
V . R E J H O L E C , V . V I T U L O V A a n d J . V A C H T E N H E I M
Contents
C i r c a d i a n a n d a b o u t - 7 - d a y ( c i r c a s e p t a n ) c a r d i o v a s c u l a r V a r i a t i o n u n d e r t r e a t m e n t w i t h t h e ß-adrenergic b l o c k e r P e n b u t o l o l
F . H A L B E R G , E . H A L B E R G , F . C A R A N D E N T E a n d E . H A U S
Section 8 — (A) Toxicology and (B) Aspects of Chronotherapeutics
C h a i r m e n : M . K N A P P ( N o t t i n g h a m , E n g l a n d ) I. A S H K E N A Z I ( T e l A v i v , Israe l )
C h r o n o t h e r a p e u t i c s — t h e i m p o r t a n c e of t h e i n d i v i d u a l a n d t h e n e e d for a n i n d i v i d u a l a p p r o a c h i n t h e r a p e u t i c t r i a l s a n d i n t h e r a p y
M . S. K N A P P
C h r o n o b i o a s s a y of r a d i a t i o n i n j u r y i n m i c e w i t h a n d w i t h o u t t i m e sh i f t
B . J . A R B O G A S T a n d A . L . G E R B E S
I n f l u e n c e o f t i m e of e x p o s u r e t o c a r b o n t e t r a c h l o r i d e o n t o x i c l i v e r i n j u r y
J . V . B R U C K N E R , R. L U T H R A , G . M . K Y L E , S. M U R A L I D H A R A , R. R A M A N A T H A N a n d D. A C O S T A
T i m e d e p e n d e n t m e r c u r i c Chloride i n d u c e d a c u t e renal failure i n r a t s a n d m i c e
J . C . C A L a n d J . C A M B A R
C i r c a d i a n v a r i a t i o n s i n t h e a c u t e t o x i c i t y o f t h r e e a m i n o g l y c o s i d e s : g e n t a m i c i n , d i b e k a c i n a n d n e t i l m i c i n i n mice
C. P A R I A T , J . C A M B A R a n d P H . C O U R T O I S
E f f e c t s of c i r c a d i a n r h y t h m o n k a n a m y c i n i n d u c e d h e a r i n g l o s s
J . F I S C H , A . Y O N O V I T Z a n d M . S M O L E N S K Y M u r i n e c i r c a d i a n v a r i a t i o n s i n s u s c e p t i b i l i t y to 4 a - d e m e t h y l -epipodophyl lotoxin-ß-D -ethyl idene g l u c o s i d e ( V P 16 -213 ) as w e l l as to t h e s o l v e n t a l o n e i n w h i c h i t w a s s u s p e n d e d
T . H . T S A I a n d L . E . S C H E V I N G
C i r c a d i a n v a r i a t i o n s i n t h e r e s p o n s e t o h y p o x i a s t u d i e s i n a n i m a l s a n d m a n
C . H E C K M A N N a n d A . H A R I R I
xxiv Contents
T i m e - r e l a t e d e f fects of h a z a r d o u s f ac to rs ( h y p o x i a , h y p e r b a r i s m , etc.) o n c i r c a d i a n r h y t h m s of a s e t o f P h y s i o l o g i e v a r i a b l e s i n h e a l t h y y o u n g m a l e s 397
I. E . A S H K E N A Z I , J . R Y B A K a n d C. H A R E L In f l u ence of s o d i u m m i n e r a l waters o n t h e c i r c a d i a n Variation of u r i n e exeretions 399
C H R . G U T E N B R U N N E R , K. F . H O L T Z , B . M Ü L L E R a n d M . P E T R I
C h r o n o b i o l o g i c a l a s p e c t s of p h y s i c a l eure t r e a t m e n t 403 G . H I L D E B R A N D T
C h r o n o b i o l o g i c a l a p p r o a c h t o t h e t r e a t m e n t of Cluster h e a d a c h e b y l i t h i u m carbonate 407
E . F E R R A R I , P. A . B O S S O L O , G . B O N O , G . M I C I E L I , A . V A I L A T I , L. M A G N A N I , E . M A R T I G N O N I a n d G . N A P P I
C i r c a d i a n a n d c i r c a s e p t a n a s p e c t s of m a l a r i a l i n f e c t i o n a n d c y c l o s p o r i n e t r e a t m e n t i n m i c e 411
S. S A N C H E Z D E L A P E N A , P. W O O D , E . H A L B E R G , G . C O R N E L I S S E N , J . E A T O N a n d F. H A L B E R G
A u t h o r I n d e x 4 1 5
Sub j e c t I n d e x 4 1 9
CIRCADIAN D Y S R H Y T H M I A IN THE BEHAV IOR OF EPILEPTIC CHILDREN WITH C L O N A Z E P A M AND/OR P H E N O B A R B I T A L T R E A T M E N T M. Hallek,*1** B. Arbogast,* T. Hellbrügge,* R. Schmid,* H. Arbogast* and B. Kleiser*
*Institute für Soziale Pädiatrie, Universität München, F.R.G. * *ER . No 105 de Chronobiologie Humaine du CNRS, Fondation A. de Rothschild, Paris, France
ABSTRAGT To evaluate the i n f l u e n c e of an t i c o n v u l s a n t s (clonazepam and phenobarbital) on behavior rhythms of c h i l d r e n , f i f t e e n 24-hr-observations with 1 Observation u n i t per minute of the behavior of 3 healthy c h i l d r e n without treatment and 12 e p i l e p t i c c h i l d r e n w i t h phenobarbital and/or clonazepam treatment were performed on standardized h o s p i t a l terms f o r s e v e r a l behavior Parameters. The r e s u l t s demonstrate that clonazepam might cause grave c i r c a d i a n dysrhythmias, whereas phenobarbital does not a l t e r c i r c a d i a n behavior rhythms to the same exten
KEYWORDS P e t i t mal e p i l e p s y , c h i l d r e n , behavior, clonazepam, phenobarb i t a l , c i r c a d i a n dysrhythmia.
INTRODUCTION In c l i n i c a l p r a c t i c e , a l t e r a t i o n s of the sleep-waking c y c l e (drowsiness) or of other behavior components are quite often observed s i d e e f f e c t s of a n t i c o n v u l s i v e medication. Neverthe-l e s s , some authors (Chemburkar, 1976) suggested that a n t i c o n v u l s i v e e f f e c t s of these drugs should be considered i s o l a t e d l y from sedative side e f f e c t s , the side e f f e c t s disappearing a f t e r a w h i l e of drug a d m i n i s t r a t i o n . Therefore, the present study i s an attempt to qu a n t i f y the oft e n f a t a l s i d e e f f e c t s i n the behavior of long-term t r e a t e d e p i l e p t i c c h i l d r e n by systematic c l i n i c a l 24-hr observations.
METHODS Subj e c t s ; Three groups of c h i l d r e n with i n f a n t i l e spasms (a p e t i t mal e p i l e p s y ) were s t u d i e d . A l l e p i l e p t i c c h i l d r e n r e c e i v e d a n t i c o n v u l s i v a n t s i n non-toxic plasmatic ranges. The f i r s t group C consisted of 3 p a t i e n t s who were tr e a t e d by clonazepam only (mean age + S.E.M. 14 + 4.6 months, 2 female ( f ) 1 male (m)), the second group PC cons i s t e d of 6 p a t i e n t s who
37
38 M. Hallek e t a l .
got a combination of phenobarbital and clonazepam (mean age of 13.3 + 1.8 months, 4 f, 2m) and the t h i r d group P consisted of 3 c h i l d r e n who received phenobarbital only (mean age of 14.7 + 6.1 months, 1 f, 2m). A c o n t r o l group (Co) of 3 healthy sub-j e c t s d i d not receive any treatment. Procedures: A l l c h i l d r e n were observed w i t h Observation u n i t e s of 1 min. by a t r a i n e d team of four persona on standardized hos-p i t a l terms w i t h i n a 24-hr time span f o r 30 behavior parameters defined p r e c i s e l y beforehand. Only seven parameters (with highest incidence) were analysed by S t a t i s t i c a l methods: I n c i -dence of sleep, r e s t l e s s n e s s , o c u l a r s e i z u r e s , e p i l e p t i c s e i -zures, weeping/crying, s i n g i n g or s i m i l a r sounds, arm movementa Nearly a l l c h i l d r e n got medication r e g u l a r l y every 8 hrs (at 0700, 1500, 2200), and there was no d i f f e r e n c e to be found i n c h i l d r e n with irregulär and regulär medication scheme, whose r e s u l t s were therefore combinecl. Food intake hours (at 0700-0730, 1130-1200, 1600-1630) were a l s o taken i n t o account, but don't seem to i n f l u e n c e the r e s u l t s . Plasmatic drug l e v e l s were c o n t r o l l e d at 10.00 a. m. on the f i r s t day of the 24-hr Observ a t i o n . A continuous plasma drug l e v e l monitoring was impossi-ble f o r t e c h n i c a l and e t h i c a l reasons.
Analyses and c a l c u l a t i o n s : Hourly data were analysed by the Single cosinor method wi t h t r i a l periods ( t) = 24, 12, 8, 6 and 4 hrs f o r each parameter, each p a t i e n t and each group. Basing on these r e s u l t s , the rhythm d e t e c t i o n r a t e was c a l c u l a t e d f o r the r e s p e c t i v e groups and periods by d i v i d i n g the number (n) of rhythm detections to be found by the c o s i n o r (with p<0.05) by the t o t a l of the t h e o r e t i c a l l y p o s s i b l e d e t e c t i o n s ( a l l i n -v e s t i g a t e d parameters ( i ) • members of the group (m)):
n i • m
The rhythm d e t e c t i o n values ( i n %) were compared by the X z - t e s t f o r e v a l u a t i n g a s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e among the four groups.
RESULTS Figures 1 - 4 show the raw data and best f i t t i n g c o s i n o r curve f o r the sleep incidence of the 3 t r e a t e d groups and the c o n t r o l group. The c o n t r o l group shows a higher amplitude than a l l groups with a n t i c o n v u l s i v e treatment and only a c i r c a d i a n sleep rhythm, whereas the groups C, PC and P e x h i b i t u l t r a d i a n sleep rhythms of which the 8-hr period i n the group PC has to be con-sidered as anormal i n t h i s age (Hellbrügge,1964). Concerning the amplitude, no l a r g e r d i f f e r e n c e can be seen among the S i n gle treatment groups. In f i g u r e 5 the rhythm d e t e c t i o n r a t e resumes the r e s u l t s i n an i n s t r u c t i v e manner: While phenobarbital r e s u l t s are hardly d i f f e r e n t from the c o n t r o l group, the groups PC and C (with combined or S i n g l e clonazepam treatment) show th a t the c i r c a dian component of the behavior (7 parameters!) has mostly (PC) or t o t a l l y (C) disappeared and that p a t h o l o g i c a l 8-hr rhythms are p e r s i s t i n g despite of the age of more than 1 year (group PC) or have even become predominant (group C). I t i s a l s o i m p r e s s i v e l y demonstrated ( c o n t r o l group) that u l t r a d i a n rhythms should normally have been disappeared i n t h i s age
G R O U P C
0 6 1? 18 0 h m > -inhrs
G R O U P P C S L E E P
I?
1-4. Sleep i n c i dence. Raw data and best f i t t i n g c o s i n o r curves. Control group (p<0 . 0 0 0 f o r t = 24 h ) , group P ( p < 0 . 0 1 / 0 . 0 5
\ f o r r = 24/ 1 2 h ) , group :. C ( p < 0 . 0 5 / 0 . 0 0 0 f o r t = = 24/ 1 2 h), group PC ( p < 0 . 0 0 0 / 0 . 0 5 / 0 . 0 1 f o r
T = 24/12/8 h). Q Time
in hrs
F i g . 5 . Rhythm d e t e c t i o n rate i n X Z-test: period (T) d. f. p
24 ( h ) 1 2(h) 8 ( h )
^ . 0 2 5 ^ . 1
R h V , h m T 0 T A L R H Y T H M D E T E C T I O N detect ion j 'or 7 b e h a v i o r p a r a m e t e r s . (p<0.05) , a , e "Single c o s i n o r m e t h o d .
0.'.-
n i im
n ! I I I
n \ P e r i o d m h r s — - 2^ 12
PC ,21 12 5, ,iu 12 3,
P C O
40 M. Hallek et a l .
ränge (with the exception of small 12-hr rudiments to admit). DISCUSSION
Previous s t u d i e s by Hellbrügge (1963, 1974), Parmelee (1961) and others showed that p h y s i o l o g i c a l and b e h a v i o r a l parameters g r a d u a l l y become c i r c a d i a n rhythmic a f t e r a few days ( e l e c t r i c s k i n r e s i s t a n c e i n the f i r s t week, Hellbrügge 1963). Thus, the sleep-waking c y c l e normally gets a c i r c a d i a n Organisation a t the age of 1 - 7 months. In t h i s study we found c i r c a d i a n dysrhythmias i n c h i l d r e n v/ith i n f a n t i l e spasms t r e a t e d by a n t i c o n v u l s a n t s which could be due to 1. the e p i l e p t i c disease or the often a s s o c i a t e d c e r e b r a l d i s o r d e r , or 2. the a n t i c o n v u l s i v e medication. The f i r s t hypo-t h e s i s cannot t o t a l l y be r e j e c t e d , but does not seem probable because of the d i f f e r e n c e s we found among the phenobarbital and the clonazepam groups. Therefore we suggest that clonazepam i s i s able to cause grave c i r c a d i a n dysrhythmias and anormal 8-hr rhythms i n the behavior of c h i l d r e n . P h e n o b a r b i t a l , however, seems to be an a n t i c o n v u l s i v e drug which does not i n f l u e n c e c i r c a d i a n rhythms of the behavior and the sleep-waking c y c l e . Further s t u d i e s w i t h a l a r g e r number of p a t i e n t s are suggested to e s t a b l i s h a reasonable chronotherapy with a n t i c o n v u l s i v e drugs and above a l l clonazepam. In t h i s way, the f a t a l side e f f e c t s which often augment the s o c i a l and mental i s o l a t i o n of these p a t i e n t s already handicapped by t h e i r d isease, could be diminished (together w i t h an e v e n t u a l l y augmented e f f i c a c y of a n t i c o n v u l s a n t s ) .
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H a l l e k , M., Reinberg, A. et a l . (1983). C i r c a d i a n and u l t r a d i a n rhythms i n behavior and s e i z u r e s i n c h i l d r e n w i t h p e t i t mal e p i l e p s y . Chronobiologia,10, p. 131.
Hellbrügge, T., Lange, J . et a l . (1963). Über das Entstehen e i ner 24-Stunden-Periodik p h y s i o l o g i s c h e r Funktionen im Säuglingsalter. F o r t s c h r . Med. 81, 19.
Hellbrügge, T. (1974). The development of c i r c a d i a n and u l t r a dian rhythms of premature and f u l l - t e r m i n f a n t s . In: L.E. Scheving, F. Halberg et a l . (Eds.), Chronobiology , pp. 339 - 341.
Janz, D. (1974). E p i l e p s y and the sleep-waking c y c l e . In: P. J . Vinken and G.W. Bruyn (Eds), Handbook of C l i n i c a l Neuro-l°gy> V o l . 15, The E p i l e p s y , Amsterdam, pp. 457 - 490.
Parmelee, A.H. (1961). A study of one i n f a n t from b i r t h to 8 month of age. Act. paed, scand. 50, pp. 160 - 170.