poison & drug information bulletin · poison & drug information bulletin july-september...

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POISON & DRUGPOISON & DRUGPOISON & DRUGPOISON & DRUGPOISON & DRUG

INFORMATION BULLETININFORMATION BULLETININFORMATION BULLETININFORMATION BULLETININFORMATION BULLETIN July-September 2005 Vol.13, No.3

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To⌧Case Conference.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .To⌧Case Conference.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .To⌧Case Conference.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .To⌧Case Conference.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .To⌧Case Conference.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2727272727

Acute orphenadrine poisoning

Cytochrome P450 Drug Interaction Table......................................Cytochrome P450 Drug Interaction Table......................................Cytochrome P450 Drug Interaction Table......................................Cytochrome P450 Drug Interaction Table......................................Cytochrome P450 Drug Interaction Table...................................... 3030303030

(updated ☺une 2005)

General Principle of Drug Interaction...............................................General Principle of Drug Interaction...............................................General Principle of Drug Interaction...............................................General Principle of Drug Interaction...............................................General Principle of Drug Interaction............................................... 3333333333

page P&D Information Bulletin / Vol. 13, No. 3, 2005

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â·ÃÈÑ¾·ì:â·ÃÈÑ¾·ì:â·ÃÈÑ¾·ì:â·ÃÈÑ¾·ì:â·ÃÈÑ¾·ì: 0-2354-7272, 0-2201-10830-2354-7272, 0-2201-10830-2354-7272, 0-2201-10830-2354-7272, 0-2201-10830-2354-7272, 0-2201-1083

Hotl ine:Hotl ine:Hotl ine:Hotl ine:Hotl ine: 13671367136713671367

â·ÃÊÒÃ:â·ÃÊÒÃ:â·ÃÊÒÃ:â·ÃÊÒÃ:â·ÃÊÒÃ: 0-2201-10840-2201-10840-2201-10840-2201-10840-2201-1084

Emai l :Emai l :Emai l :Emai l :Emai l : [email protected]@[email protected]@[email protected]

Website:Website:Website:Website:Website: www.ra.mahidol.ac.th/poisoncenter/ www.ra.mahidol.ac.th/poisoncenter/ www.ra.mahidol.ac.th/poisoncenter/ www.ra.mahidol.ac.th/poisoncenter/ www.ra.mahidol.ac.th/poisoncenter/

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To⌧Case ConferenceTo⌧Case ConferenceTo⌧Case ConferenceTo⌧Case ConferenceTo⌧Case Conference

¼ÙéªÒÂä·ÂâÊ´ ÍÒÂØ 24 »Õ ÀÙÁÔÅÓà¹Ò ¡ÃØ§à·¾Ï ¹Ñ¡ÈÖ¡ÉÒ

ÍÒ¡ÒÃÊÓ¤Ñ: ¾Ù ¤ØÂÊÑºÊ¹ ¡èÍ¹ÁÒâÃ§¾ÂÒºÒÅ 8 ªÑèÇâÁ§

»ÃÐÇÑµÔ»Ñ ØºÑ¹: 10 ªÑèÇâÁ§¡èÍ¹ÁÒâÃ§¾ÂÒºÒÅ ¼Ùé»èÇÂ¾Ù´â·ÃÈÑ¾·ì¡Ñºà¾×èÍ¹ ºÍ¡ÇèÒ¡Ô¹ÂÒ¤ÅÒÂ¡ÅéÒÁà¹×éÍ 1 «Í§

äÁè·ÃÒº¨Ó¹Ç¹·Õèá¹è¹Í¹

8 ªÑèÇâÁ§¡èÍ¹ÁÒâÃ§¾ÂÒºÒÅ ÒµÔ¾ºÇèÒ¼Ùé»èÇÂÁÕÍÒ¡ÒÃÇØè¹ÇÒÂ ¾Ù ¨ÒÊÑºÊ¹ Â×¹¢Öé¹àÍ§äÁèäËÇ áµèÊÒÁÒÃ¶¢ÂÑº

á¢¹¢Òä»ÁÒàÍ§ä é ÁÕÍÒ¡ÒÃËÇÒ´ÃÐáÇ§ Ö§¹ÓµÑÇÊè§âÃ§¾ÂÒºÒÅ

ÂÒ·Õè¼Ùé»èÇÂ¡Ô¹à»ç¹¢Í§áÁè ã¹¶Ø§ÂÒ»ÃÐ¡Íº éÇÂ ibuprofen, piroxicam, ranitidine áÅÐ orphenadrine

µÃÇ¨ÃèÒ§¡ÒÂ: PR 112/min, BP 130/80 mmHg, RR 20/min, BT 36oC

¼Ùé»èÇÂÅ×ÁµÒàÍ§ µÍº¤Ó¶ÒÁáÅÐ·ÓµÒÁ¤ÓÊÑè§ä éà»ç¹ºÒ§¤ÃÑé§ ÁÕ·èÒ·ÕËÇÒ´ÃÐáÇ§

Pupils 3 mm react to light both eyes, confusion, motor power grade 4, grossly intact

Barbinskis� sign: absence, stiff neck: negative

Dry lip, tongue and oral mucosa

Heart: tachycardia, regular rhythum, normal S1 S

2 , no murmur

Lung: clear, equal both sides

Abd: decrease bowel sound, full urinary bladder

Extremities: hestitation marking at left forearm

µÃÇ¨·Ò§ËéÍ§»¯ÔºÑµÔ¡ÒÃ:

CBC: Hct 49.2%, Hb 17g/dL, WBC 10,000µL, Plt 208,000/µL

Glu: 108 mg/dL, BUN/Cr: 7 /1.1 mg/dL

Electrolyte: Na 141, K 3.44, Cl 105, CO2.19.8 mmol/L

Alb 48.1 g/L, Ca 9.0 mg/dL, Mg 2.1 mg/dL

Problem lists:

1. Alteration of consciousness

2. History of drugs overdose

3. Passive compulsive disorder

¹ÒÂá¾·ÂìÊÁÂÈ Ç§È¡Ã¾Ñ²¹Ò*

ÃÍ§ÈÒÊµÃÒ¨ÒÃÂì¹ÒÂá¾·ÂìÇÔ¹ÑÂ Ç¹Ò¹Ø¡ÙÅ*á¾·Âì»ÃÐ¨ÓºéÒ¹ ÀÒ¤ÇÔªÒàÇªÈÒÊµÃì©Ø¡à©Ô¹¤³Ðá¾·ÂÈÒÊµÃìâÃ§¾ÂÒºÒÅÃÒÁÒ¸Ôº´Õ


¼Ùé»èÇÂÃÒÂ¹ÕéÁÕÀÒÇÐ¢Í§¡ÒÃà»ÅÕèÂ¹á»Å§¢Í§ÃÐ´Ñº¤ÇÒÁÃÙéÊÖ¡ÍÂèÒ§©Ñº¾ÅÑ¹ (acute alteration of consciousness) â´Â·Õè¼Å¡ÒÃµÃÇ¨ÃèÒ§¡ÒÂäÁè¾º localizing sign ·ÓãËéµéÍ§¤Ô´¶Ö§ÊÒàËµØ·Õèà¡Ô´¨Ò¡ metabolic ËÃ×Í toxic substance ÁÒ¡¡ÇèÒÀÒÇÐ·ÕèÁÕintracranial lesion »ÃÐ¡Íº¡Ñº¼Ùé»èÇÂÁÕÍÒ¡ÒÃáÊ´§·ÕèÊÓ¤Ñ¤×ÍªÕ¾¨ÃàÃçÇ »Ò¡¤ÍáËé§ ¼ÔÇË¹Ñ§áËé§ áÅÐ¤ÅÓ¡ÃÐà¾ÒÐ»ÑÊÊÒÇÐä é (uri-nary bladder) ·Ñé§ËÁ´¹Õéà¢éÒä é¡Ñº¡ÅØèÁÍÒ¡ÒÃ �anticholinergic syn-drome� «Öè§¨ÐµéÍ§áÂ¡¨Ò¡¡ÅØèÁÍÒ¡ÒÃ �sympathomimetic syn-drome� ·ÕèÊÒÁÒÃ¶·ÓãËéà¡Ô´ÍÒ¡ÒÃÊÑºÊ¹ ÇØè¹ÇÒÂáÅÐÁÕÍÒ¡ÒÃáÊ´§¢éÒ§µé¹ä´é·Ø¡ÍÂèÒ§ Â¡àÇé¹¼ÔÇË¹Ñ§·Õè¨ÐµÃÇ¨ä´éáµ¡µèÒ§¡Ñ¹¡ÅèÒÇ¤×Íanticholinergic syndrome ¨Ð·ÓãËé¼ÔÇË¹Ñ§áËé§ ã¹¢³Ð·Õè sym-pathomimetic syndrome ¨ÐÁÕ¼ÔÇË¹Ñ§á©ÐªØèÁàË§×èÍ (µÒÃÒ§·Õè 1)¡ÒÃµÃÇ¨¼ÔÇË¹Ñ§ Ö§ÁÕ¤ÇÒÁÊÓ¤Ñã¹¡ÒÃáÂ¡ÃÐËÇèÒ§ 2 ¡ÅØèÁÍÒ¡ÒÃ¹Õé

¡ÒÃÇÔ¹Ô ©ÑÂâÃ¤ã¹¼Ùé»èÇÂÃÒÂ¹Õé¤×Í- Anticholinergic drug poisoning

¡ÒÃÇÔ¹Ô ©ÑÂáÂ¡âÃ¤¤×Í- Sympathomimetic drug poisoning- Encephalitis

1. Anticholinergic drug poisoning ÊÓËÃÑºÀÒÇÐ¹Õé ÂÒ·Õè¾ºä´éºèÍÂ ¤×ÍÂÒ¡ÅØèÁ anticholinergic áÅÐ antihistamine àªè¹chlorpheniramine, cyproheptadine, atropine, ¡ÅØèÁ¢Í§¾ÔÉ¨Ò¡¾×ª¤×Í ÅÓâ¾§ áÅÐ¡ÅØèÁàËç ¾ÔÉ àªè¹ àËç ¢Õé¤ÇÒÂ (âÍÊ¶ÅÇ§ Ôµ)à»ç¹µé¹ àÁ×èÍ¾Ô¨ÒÃ³Ò¨Ò¡ÂÒ·Õè¼Ùé»èÇÂ¡Ô¹¡ç¾ºÇèÒÂÒ orphenadrine«Öè§à»ç¹¡ÅØèÁ muscle relaxant ¡çÁÕÃÒÂ§Ò¹ÇèÒÊÒÁÒÃ¶·ÓãËéà¡Ô ¡ÅØèÁÍÒ¡ÒÃ anticholinergic ä éàªè¹à ÕÂÇ¡Ñ¹

ÊèÇ¹ÂÒ·ÕèÁÕ¡ÒÃ¡Ô¹à¡Ô¹¢¹Ò´·Õè¾ººèÍÂ¤×Í ÂÒ¡ÅØèÁ tricyclic an-tidepressants (TCA) áÅÐ¡ÅØèÁ antipsychotic àªè¹ phenothiaz-ine «Öè§¨ÐÁÕÄ·¸Ôì anticholinergic ÃèÇÁ´éÇÂáÅÐà»ç¹ÍÒ¡ÒÃáÊ´§·ÕèÊÓ¤Ñ«Öè§ªèÇÂã¹¡ÒÃÇÔ¹Ô ©ÑÂÀÒÇÐà»ç¹¾ÔÉ¨Ò¡ÂÒ 2 ¡ÅØèÁ¹Õé â´Â¼Ùé»èÇÂ·Õèä´éÃÑº¾ÔÉÁÑ¡ÁÒ´éÇÂÍÒ¡ÒÃËÁ´ÊµÔËÃ×ÍÃÐ´Ñº¤ÇÒÁÃÙéÊÖ¡µÑÇÅ´Å§ÃèÇÁ¡ÑºÍÒ¡ÒÃáÅÐÍÒ¡ÒÃáÊ´§¢Í§ anticholienrgic ÁÒ¡¡ÇèÒ¨Ðà»ç¹ÊÑºÊ¹ ÇØè¹ÇÒÂàËÁ×Í¹¼Ùé»èÇÂÃÒÂ¹Õé ´Ñ§¹Ñé¹ã¹¼Ùé»èÇÂÃÒÂ¹Õé¨Ö§äÁè¤Ô´¶Ö§ÊÒàËµØ Ò¡ÂÒ 2 ¡ÅØèÁ¹ÕéÁÒ¡¹Ñ¡

2. Amphetamines áÅÐÍ¹Ø¾Ñ¹ Øì àªè¹ ÂÒºéÒ (methamphet-amine) ÂÒÍÕ (Ectasy, methylenedioxy methamphetamine,MDMA) à»ç¹ÊÒÃ·ÕèÍÍ¡Ä· Ôì sympathomimetic ÊÒÁÒÃ¶·ÓãËéÃÐ Ñº¤ÇÒÁÃÙéÊÖ¡à»ÅÕèÂ¹á»Å§ ËÑÇã¨àµé¹àÃçÇ ÊÑºÊ¹ ËÇÒ´ÃÐáÇ§ áÅÐà»ç¹ÊÒÃàÊ¾µÔ ·Õè¾ººèÍÂ áµè·ÕèäÁèà¢éÒ¡ÑºÍÒ¡ÒÃáÅÐÍÒ¡ÒÃáÊ´§¢Í§¼Ùé»èÇÂ¤×Í amphetamine toxicity ÊèÇ¹ãËè¾ºÇèÒÁÕàË§×èÍÍÍ¡ÁÒ¡

ÃèÇÁ éÇÂ3. Encephalitis ¼Ùé»èÇÂ·ÕèÁÕÀÒÇÐ¢Í§ÃÐ Ñº¤ÇÒÁÃÙéÊÖ¡·Õèà»ÅÕèÂ¹

á»Å§ÊÑºÊ¹à©ÕÂº¾ÅÑ¹ ËÃ×ÍÁÕÍÒ¡ÒÃ·Ò§¨Ôµ»ÃÐÊÒ··Õèà¡Ô´¢Öé¹ãËÁè¨Óà»ç¹µéÍ§ÇÔ¹Ô ©ÑÂáÂ¡ÀÒÇÐ encephalitis éÇÂâ´Âà©¾ÒÐã¹ÃÒÂ¢Í§¼Ùé»èÇÂà¹×èÍ§¨Ò¡ encephalitis ÍÒ¨ÊÒÁÒÃ¶à¡Ô ¨Ò¡¤ÇÒÁ¼Ô »¡µÔ¢Í§cholinergic outflow ·ÓãËéà¡Ô anticholinergic syndrome ¢Öé¹ä éáµèã¹¼Ùé»èÇÂÃÒÂ¹ÕéÁÕ»ÃÐÇÑµÔ¡ÒÃ¡Ô¹ÂÒ anticholinergic ·ÕèªÑ´à¨¹·ÓãËé¤Ô ¶Ö§ encephalitis ·ÕËÅÑ§

¡ÒÃÃÑ¡ÉÒàº×éÍ§µé¹ËÅÑ§¨Ò¡»ÃÐàÁÔ¹ªèÍ§·Ò§¡ÒÃËÒÂã¨ ¡ÒÃËÒÂ-ã¨ áÅÐ¡ÒÃäËÅàÇÕÂ¹âÅËÔµ (Airway, Breathing, Circulation;ABC) áÅÐ vital signs áÅéÇ¾ºÇèÒÍÂÙèã¹à¡³±ì»¡µÔ áµèËÑÇã¨àµé¹àÃçÇáÅÐÁÕ confusion ·ÓµÒÁ¤ÓÊÑè§ä éà»ç¹ÊèÇ¹ãËè

ÂÒ orphenadrine à»ç¹ muscle relaxant ÍÍ¡Ä· Ôìã¹ 1 ªÑèÇâÁ§ËÅÑ§ÃÑº»ÃÐ·Ò¹ ÃÐ ÑºÂÒ¢Öé¹ÊÙ§ÊØ »ÃÐÁÒ³ 6 � 8 ªÑèÇâÁ§ ÁÕ¤èÒ¤ÃÖè§ªÕÇÔµ (half�life) 14�16 ªÑèÇâÁ§ ÊÒÁÒÃ¶·ÓãËéà¡Ô anticholin-ergic syndrome, psychosis, seizure, confusion áÅÐ myoglo-binuria ä é

¡ÒÃÃÑ¡ÉÒ¼Ùé»èÇÂ·Õèä éÃÑº anticholinergic substance »ÃÐ¡ÍºéÇÂ GI decontamination éÇÂ activated charcoal ¾ºÇèÒä é

»ÃÐâÂª¹ì á¼¹¡ÒÃÃÑ¡ÉÒâ´ÂÃÇÁ ¤×Í ÃÑ¡ÉÒµÒÁÍÒ¡ÒÃáÅÐ¡ÒÃÃÑ¡ÉÒáºº»ÃÐ¤Ñº»ÃÐ¤Í§ ¶éÒ¼Ùé»èÇÂÁÕÍÒ¡ÒÃÊÑºÊ¹ËÃ×Í¡ÃÐÊÑº¡ÃÐÊèÒÂÁÒ¡ÍÒ¨¨Ð¾Ô ÒÃ³ÒãËéÂÒ¡ÅØèÁ benzodiazepine à¾×èÍ¤Çº¤ØÁÍÒ¡ÒÃ¢Í§¼Ùé»èÇÂã¹ÃÐÂÐ¹Õé

ÊÓËÃÑº¼Ùé»èÇÂ·ÕèÁÕÍÒ¡ÒÃ anticholinergic syndrome ÍÒ¨¨ÐµÃÇ¨¤Å×è¹ä¿¿éÒËÑÇã¨ ( EKG) ËÒÇèÒÁÕÀÒÇÐ right axis deviation,widening QRS, prolonged QT, prolonged PR à¡Ô ¢Öé¹ËÃ×ÍäÁèà¾ÃÒÐà»ç¹ÀÒÇÐá·Ã¡«éÍ¹·Õè¾ºä éºéÒ§ã¹¡Ã³Õ·Õèà»ç¹¾ÔÉ¨Ò¡ antihis-tamine áµèäÁèºèÍÂ ¢éÍ¾Ö§ÃÐÇÑ§¤×Í orphenadrine ÁÑ¡¼ÊÁ¡Ñºparacetamol ã¹àÁç´à´ÕÂÇ¡Ñ¹ ©Ð¹Ñé¹¨ÐµéÍ§¤Ó¹Ö§ÇèÒÍÒ¨¨ÐÁÕÀÒÇÐparacetamol overdose ÃèÇÁ éÇÂ ËÒ¡ÁÕ¡ç¤ÇÃ¾Ô ÒÃ³ÒÃÑ¡ÉÒàÃ×èÍ§paracetamol overdose éÇÂ

à¹×èÍ§¨Ò¡¼Ùé»èÇÂ¡Ô¹ÂÒÁÒ»ÃÐÁÒ³ 8 ªÑèÇâÁ§¡èÍ¹ÁÒâÃ§¾ÂÒºÒÅ

¼Å¡ÒÃµÃÇ¨·Ò§ËéÍ§»¯ÔºÑµÔ¡ÒÃ¾ÔÉÇÔ·ÂÒ:Urine amphetamine: negativeBlood screening for drug and pesticide (ÇÔ¸Õ Rapid

Emergency Drug Identification, REMEDI): orphenadrine 1.56µg/ml (Toxic range >0.50 µg/ml)¡ÒÃÇÔ¹Ô ©ÑÂ¼Ùé»èÇÂÃÒÂ¹Õé¤×Í acute orphenadrine poisoning

28

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¡ÒÃ·Ó gastric lavage äÁèä é»ÃÐâÂª¹ì áÁéÇèÒ anticholinergiceffect Ð delay gastric emptying time ¡çµÒÁ ¼Ùé»èÇÂ Ö§ä éÃÑºà¾ÕÂ§activated charcoal 50 g ·Ò§ NG tube áÅÐ¼Ùé»èÇÂÊÑºÊ¹äÁèÁÒ¡ä éãËé diazepam ã¹¢¹Ò´äÁèÊÙ§ÁÒ¡à¾×èÍãËé¼Ùé»èÇÂÊ§ºÅ§áÅÐ¾Ñ¡ä é

ËÅÑ§ÃÑºäÇéã¹âÃ§¾ÂÒºÒÅ 1 ÇÑ¹ (ËÅÑ§¡Ô¹ÂÒ»ÃÐÁÒ³ 40 ªÑèÇâÁ§)¼Ùé»èÇÂÊÑºÊ¹¹éÍÂÅ§ µÍº¤Ó¶ÒÁä é Õ áµèÂÑ§ÁÕÍÒ¡ÒÃ»Ò¡áËé§ ¤ÍáËé§¼ÔÇáËé§ pupils 5 mm react to light both eyes à¹×èÍ§¨Ò¡â´Â»¡µÔáÅéÇÂÒÊèÇ¹ãËè·ÕèÍÍ¡Ä· Ôì anticholinergic effect ËÅÑ§¨Ò¡¼Ùé»èÇÂä´éÃÑº¡ÒÃÃÑ¡ÉÒÍÒ¡ÒÃÁÑ¡¨Ð´Õ¢Ö é¹áÅÐËÒÂä»ã¹ 24�48 ªÑèÇâÁ§ËÅÑ§¡Ô¹ áµèã¹¼Ùé»èÇÂÃÒÂ¹Õéä´éÃÑº»ÃÐ·Ò¹ÂÒ orphenadrine «Öè§ÍÍ¡Ä· Ôì¤èÍ¹¢éÒ§¹Ò¹ Ö§ÂÑ§¾º anticholinergic symptoms àËÅ×ÍÍÂÙè ËÅÑ§¨Ò¡ÃÑ¡ÉÒáºº»ÃÐ¤Ñº»ÃÐ¤Í§ (supportive treatment)¼Ùé»èÇÂ¡ÅÑºà»ç¹»¡µÔáÅÐãËé¡ÅÑººéÒ¹ä éËÅÑ§¨Ò¡ÃÑºäÇéã¹âÃ§¾ÂÒºÒÅ 3ÇÑ¹ áÅÐä´é»ÃÖ¡ÉÒ¨Ôµá¾·Âìà¾×èÍ»ÃÐàÁÔ¹ÍÒ¡ÒÃ¼Ùé»èÇÂà¾ÃÒÐ¤Ô´ÇèÒ¼Ùé»èÇÂÁÕ psychiatric problem ¨Ôµá¾·ÂìãËé¡ÒÃÇÔ¹Ô¨©ÑÂÇèÒà»ç¹adjustment disorder, depressed mood áÅÐ suicidal attemptÖ§ä éãËé¼Ùé»èÇÂ¡ÅÑººéÒ¹áÅÐ¹Ñ ÁÒµÃÇ¨à¾×èÍµÔ µÒÁ¼Å¡ÒÃÃÑ¡ÉÒµèÍä»

àÍ¡ÊÒÃ»ÃÐ¡Íº¡ÒÃàÃÕÂºàÃÕÂ§1.Wax PM. Anticholinergic toxicity. In: Tintinalli JE, KelenGD, Stapczynski JS, editors. Emergency Medicine: A com-

prehensive study guide. 6th ed. New York: McGraw-Hill,2004. p. 1143 �1146.2. Ma OJ. Anticholinergic toxicity. In: Ma OJ, Cline DM.Emergency Medicine Manual. 6th ed. New York: McGraw�Hill, 2004. p.476 � 478.3. Schauben JL. Muscle relaxants. In: Ford MD, Delany KA,Ling LJ, Erickson T, editors. Clinical Toxicology. Philadel-phia: W.B. Saunders Company, 2001. p. 289 � 295.4. Leikin JB, Paloucek FP. Poisoning&Toxicology Compen-dium with Symptoms Index. Ohio: Lexi-Comp Inc.,1998. p427 � 4285. Hurlbut KM. General muscle relaxants. In: Dart RC, editor.Medical toxicology. 3 rd ed. Philadelphia: Lippincott Williams& Wilkins, 2004. p.598 � 600.6. Bruns JJ.(2005) Toxicity, Anticholinergic. [Online] Avail-able: http://www.eMedicine.Com. [2005, September 22].

Toxidrome Anticholinergic Sympathomimetic

Vital signs HR, BP, T HR, BP, T

Mental status Agitation, lethargy, coma Hyperactive, psychosis, agitation

Symptoms Blurred vision, hallucination Hyperalertness, seizure

Signs Dry skin & mucosa, mydriasis Diaphoresis, mydriasis Bowel movement, bladder retention

Substances Antihistamines, anticholinergics, Amphetamine, methamphetamine, MDMA,Mushroom, Tricyclic antidepressants, Cocaine, phencyclidine, phenylpropanolamine,Antipsychotics Theophylline, caffeine

µÒÃÒ§·Õè 1 à»ÃÕÂºÍÒ¡ÒÃáÅÐÍÒ¡ÒÃáÊ´§ÃÐËÇèÒ§ Anticholinergic áÅÐ Sympathomimetic Toxidrome

29


CYP1A2 CYP2B6 CYP2C19SUBSTRATES amitriptyline

caffeineclomipramineclozapinecyclobenzaprineestradiolfluvoxaminehaloperidolimipramine N-DeMEmexilletinenaproxenolanzapineondansetronphenacetin=>acetaminophen =>NAPQIpropranololriluzoleropivacainetacrinetheophyllinetizanidine

verapamil[R] warfarinzileutonzolmitriptan

INHIBITORS amiodaronecimetidinefluoroquinolonesfluvoxaminefurafyllineinterferon?methoxsalenmibefradil

INDUCERS broccolibrussel sproutschar-grill meatinsulinmethyl cholanthrenemodafininafcillinbeta-naphthoflavoneomeprazoletobacco

GENETICS chromosome 15

bupropioncyclophosphamideefavirenzifosfamidemethadone

thiotepaticlopidine

phenobarbitalrifampicin

chromosome 19polymorphic3-4% Caucasians PMs

Proton Pump Inhibitors

lansoprazoleomeprazolepantoprazoleE-3810Anti-epileptics

diazepam=> Norphenytoin[O]S-mephenytoinphenobarbitone

chloramphenicalcimetidinefelbamatefluoxetinefluvoxamineindomethacinketoconazolelansoprazole

carbamazepinenorethindroneNOT pentobarbitalprednisonerifampin

chromosome 10polymorphic3-5% Caucasians PMs

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30

Cytochrome P450 Drug Interaction Table (updated: ☺une 2005)

CYP2C8amodiaquinecerivastatinpaclitaxelrepaglinidetorsemide

trimethoprimgemfibrozilglitazonesquercetinmontelukast

rifampicin

chromosome 10

page

CYP2D6

SUBSTRATES NSAIDs

diclofenacibuprofenmeloxicamS-naproxen=>NorpiroxicamsuprofenSulfonylureas

glyburide/glibenclamideglipizideglimepiridetolbutamide

INHIBITORS amiodaronefluconazolefluvastatinfluvoxamineisoniazidlovastatinphenylbutazoneprobenicidsertralinesulfamethoxazolesulfaphenazoleteniposidetrimethoprimzafirlukast

INDUCERS rifampinsecobarbital

GENETICS chromosome 10polymorphic1-3% Caucasian PMs

Beta Blockers

carvedilolS-metoprololpropafenonetrimololAntidepressants

amitriptylineclomipraminedesipramineimipramineparoxetineAntipsychotics

haloperidolperphenazinerisperidone=>9OHthioridazine

alprenololamphetaminearipiprazole

atomoxetine

bufuralolchlorpheniraminechlorpromazinecodeine[=>O-desMe]

amiodaronebuproprioncelecoxibchlorpheniramine

chlorpromazinecimetidinecitalopramclomipraminecocainedoxepin

doxorubicinduloxetine

escitalopramfluoxetinehalofantrinered-haloperidollevomepromazinemetoclopramidemethadonemibefradil

dexamethasonerifampin

chromosome 22polymorphic5-10% Caucasian PMs

Angiotensin II Blockerslosartanirbesartan

amitriptylinecelecoxibfluoxetinefluvastatinnateglinidephenytoin=>4-OHrosiglitazonetamoxifentorsemideS-warfarin

CYP2C9

debrisoquinedexfenfluraminedextromethorphanduloxetin

encainideflecainidefluoxetinefluvoxaminelidocainemetoclopramidemethoxyamphetaminemexiletineminaprinenortriptylinenebivolol

ondansetronperhexilinephenacetinphenforminpropranololsparteinetamoxifentramadolvenlafaxine

moclobemideparoxetinequinidineranitidineritonavirsertralineterbinafineticlopidine

Histamine H1 receptor

antagonists

chlorpheniramineclemastinediphenhydraminehydroxyzineperphenazinetripelennamine

31


CYP3A4,5,7

SUBSTRATES Anesthetics

enfluranehalothaneisofluranemethoxyfluranesevoflurane

acetaminophen=>NAPQIanilinebenzenechlorzoxazoneethanolN,N-dimethyl formamidetheophylline=>8-OH

INHIBITORS diethyl-dithiocarbamatedisulfiram

INDUCERS ethanolisoniazid

GENETICS chromosome 10

CYP2E1

Macrolide antibiotics

clarithromycinerythromycin [not3A5]NOT azithromycintelithromycin

Anti-arrhythmics

quinidine=>3-OH[not3A5]Benzodiazepines

alprazolamdiazepam=>3-OHmidazolamtriazolamImmune Modulators

cyclosporinetacrolimus[FK506]HIV Antivirals

indinavirnelfinavirritonavirsaquinavirProkinetic

cisaprideAntihistamines

astemizolechlorpheniramineterfenidine

HIV Antivirals

delaviridineindivinirnelfinavirritonavir

HIV Antivirals

efavirenznevirapine

chromosome 7

Calcium Channel Blockers

amlodipinediltiazemfelodipinelercanidipinenifedipinenisoldipinenitrendipineverapamilHMG CoA reductase Inhibitors

atrovastatincerivastatinlovastatinNOT pravastatinsimvastatinSteroid 6beta-OH

estradiolhydrocortisoneprogesteronetestosterone

Miscellaneous

alfentanylaripiprazole

buspironecafergotcaffeine=>TMUcilostazol

cocainecodeine-N-demethylation

amiodaroneaprepitantNOT azithromycinchloramphenicalcimetidineciprofloxacinclarithromycindiethyl-dithiocarbamatediltiazemerythromycinfluconazole

barbituratescarbamazepineglucocorticoidsmodafiniloxcarbazepinephenobarbitalphenytoin

Miscellaneous (cont.)

dapsonedextromethorphandocetaxel

domperidone

eplerenonefentanylfinasteridegleevechaloperidolirinotecanLAAMlidocainmethadonenateglinideodansetronpimozidepropranololquinineNOT rosuvastatinsalmeterolsildenafilsirolimustamoxifentaxolterfenadinetrazodonevincristinezaleplonzolpidem

fluvoxaminegestodenegrape fruit juiceitraconazoleketoconazolemifepristonenefazodonenorfloxacinnorfluoxetinemibefradilstar fruit

verapamil

pioglitazonerifabutinrifampinSt.John's worttroglitazone

32

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33

Drug interaction (DI) ËÃ×ÍÍÑ¹µÃ¡ÔÃÔÂÒ à»ç¹¡ÒÃà»ÅÕèÂ¹á»Å§¤Ø³ÊÁºÑµÔ¢Í§ÂÒµÑÇË¹Öè§ (objective drug, OD) â´Â¡ÒÃà»ÅÕèÂ¹á»Å§¹Õéà¡Ô ¨Ò¡Ä· Ôì¢Í§ÂÒ (precipitant drug) ÊÒÃà¤ÁÕ ËÃ×ÍÍÒËÒÃ·Õè¼Ùé»èÇÂä´éÃÑºÃèÇÁ¡Ñ¹¡Ñº OD ¼Å¡ÃÐ·º·Õèà¡Ô´¢Öé¹¹ÕéÍÒ¨¨ÐÁÕ¼ÅµèÍàÀÊÑª-¨Å¹ÈÒÊµÃì (pharmacokinetic) ËÃ×ÍàÀÊÑª¾ÅÈÒÊµÃì (pharmaco-dynamic) ¢Í§ OD ¡çä é â´Â¼Å¡ÃÐ·º·Õèà¡Ô ¢Öé¹¹ÕéÍÒ¨ÁÕ¼Å·Ñé§·ÓãËé¼Å¡ÒÃÃÑ¡ÉÒäÁèä é¼Å ÍÒ¨à¡Ô ¼Å¢éÒ§à¤ÕÂ§¨Ò¡ÂÒËÃ×ÍÍÒ¨äÁèÁÕ¼ÅµèÍ¡ÒÃÃÑ¡ÉÒàÅÂ¡çä é ©Ð¹Ñé¤§ÁÔãªèà»ç¹¢éÍËéÒÁã¹¡ÒÃãªéÂÒ·Ñé§ÊÍ§µÑÇÃèÇÁ¡Ñ¹àÊÁÍä» ¶éÒ DI ¹Ñé¹äÁèÁÕ¼Å¡ÃÐ·ºµèÍ¼Ùé»èÇÂÍÂèÒ§ÁÕ¹ÑÂÊÓ¤Ñ·Ò§¤ÅÔ¹Ô¡ Ñ§¹Ñé¹ËÒ¡·ÃÒºÇèÒÂÒ·Õè¼Ùé»èÇÂä éÃÑºÍÒ¨à¡Ô DI ä é¡çµéÍ§ãªéÂÒ´Ñ§¡ÅèÒÇÍÂèÒ§ÃÐÁÑ´ÃÐÇÑ§ ãËéà½éÒÊÑ§à¡µ¡ÒÃà¡Ô´¾ÔÉ¢Í§ÂÒÍÂèÒ§ÊÁèÓàÊÁÍ ¾ÃéÍÁ·Ñé§ãËé¢éÍÁÙÅá¡è¼Ùé»èÇÂ¶Ö§¼Å¢éÒ§à¤ÕÂ§·Õè Ðà¡Ô ¢Öé¹«Öè§¨Ð·ÓãËé¼Å¡ÃÐ·ºµèÍ¼Ùé»èÇÂ¹éÍÂÅ§áÅÐ·ÓãËéá¾·Âìá¡éä¢ÀÒÇÐ´Ñ§¡ÅèÒÇÍÂèÒ§·Ñ¹·èÇ§·Õ

»íËÒ¡ÒÃà¡Ô DI ËÃ×Í¡ÒÃà½éÒÃÐÇÑ§¡ÒÃà¡Ô DI ÁÑ¡à»ç¹»íËÒ·ÕèÁÑ¡¨Ð¶Ù¡ÁÍ§¢éÒÁä»ã¹¡ÒÃ ÙáÅ¼Ùé»èÇÂ ËÒ¡á¾·ÂìËÃ×ÍºØ¤ÅÒ¡Ã·Ò§¡ÒÃá¾·ÂìÃÐÅÖ¡¶Ö§áÅÐà½éÒÃÐÇÑ§¡ÒÃà¡Ô DI Ðà»ç¹ÊÔè§·Õè·ÓãËé¡ÒÃÃÑ¡ÉÒ¼Ùé»èÇÂà»ç¹ä»ÍÂèÒ§ÁÕ»ÃÐÊÔ· ÔÀÒ¾ÁÒ¡ÂÔè§¢Öé¹ ÍÂèÒ§äÃ¡çµÒÁ ÂÒ·Õèãªéã¹»Ñ ØºÑ¹ÁÕÁÒ¡ÁÒÂËÅÒÂª¹Ô ¡ÒÃ¨´¨Ó DI ¢Í§ÂÒáµèÅÐª¹Ô ÁÕ¤ÇÒÁÂØè§ÂÒ¡ ¡ÒÃãªé¢éÍÁÙÅÊÒÃÊ¹à·È (internet) ¨ÐªèÇÂãËé¢éÍÁÙÅà¡ÕèÂÇ¡ÑºDI ä´éÁÒ¡¢Ö é¹ àªè¹·Õ è www.drug-interactions.com ËÃ×Íwww.drugs.com

¡Åä¡¡ÒÃà¡Ô drug interaction¡ÒÃà¡Ô DI ¹Ñé¹ ¼Å¡ÃÐ·º·Õèà¡Ô ¢Öé¹ÍÒ¨ÁÕµèÍ pharmacoki-

netic ËÃ×Í pharmacodynamic ¢Í§ OD ¡çä é ã¹·Õè¹Õé¢ÍÍ ÔºÒÂà©¾ÒÐ pharmacokinetic drug interaction â´ÂÁÕÃÒÂÅÐàÍÕÂ´ Ñ§¹ÕéPharmacokinetic Mechanisms

ËÒ¡¤Ò´ÇèÒ¼Ùé»èÇÂà¡Ô´ÀÒÇÐ DI ¼Å¡ÃÐ·ºµèÍ OD ÁÕ¼ÅµèÍ¢ºÇ¹¡ÒÃ pharmacokinetic ¢Í§ÂÒ µéÍ§¤Ô ÇèÒ¼Å¡ÃÐ·º¹Ñé¹ÁÕ¼ÅµèÍ¢Ñé¹µÍ¹ absorption, distribution, metabolism ËÃ×Í elimi-nation (ADME) ¢Í§ OD ËÃ×ÍÁÕ¼ÅµèÍËÅÒÂ æ ¢Ñé¹µÍ¹ÃèÇÁ¡Ñ¹â´Â¾Ô ÒÃ³ÒÂÒáµèÅÐµÑÇ·ÕèãªéÃèÇÁ¡Ñº OD ÇèÒÁÕ¼ÅµèÍ¢Ñé¹µÍ¹ã´ Ö§¨ÐÊÒÁÒÃ¶ËÒ¼Å¡ÃÐ·º¢Í§¡ÒÃà¡Ô´ DI ´Ñ§¡ÅèÒÇä´éÍÂèÒ§¤ÃÍº¤ÅØÁ

General Principle of Drug Interaction

áÅÐÊÒÁÒÃ¶á¡éä¢ãËé¡ÒÃÃÑ¡ÉÒ¼Ùé»èÇÂä´éàËÁÒÐÊÁÂÔè§¢Öé¹1. Chemical interactions

à¡Ô ¢Öé¹à¹×èÍ§¨Ò¡ÂÒà¡Ô Ô¡ÔÃÔÂÒ·Ò§à¤ÁÕ ËÃ×Í·Ò§ÊÃÕÃÐ¡ÑºÂÒÍ×è¹·ÕèãËéÃèÇÁ¡Ñ¹¡èÍ¹·ÕèÂÒ¨Ð¶Ù¡ Ù «ÖÁ¨Ò¡·Ò§à Ô¹ÍÒËÒÃ ÁÕ¼Å·ÓãËéÃÐ ÑºOD ã¹àÅ×Í´Å´Å§ àªè¹ äÁè¤ÇÃ¼ÊÁÂÒ©Õ´ÊÍ§ª¹Ô´ã¹¢Ç´à´ÕÂÇ¡Ñ¹Â¡àÇé¹¨ÐÁÕ¡ÒÃ¾ÔÊÙ ¹ìÇèÒÂÒ·Ñé§ÊÍ§ª¹Ô äÁèÁÕ» Ô¡ÔÃÔÂÒ·Ò§à¤ÁÕµèÍ¡Ñ¹à·èÒ¹Ñé¹ËÃ×Í¡ÒÃËéÒÁÃÑº»ÃÐ·Ò¹ÂÒ tetracycline ¡Ñº¹Á à¾ÃÒÐ¨Ðà¡Ô » Ô¡ÔÃÔÂÒ·Ò§à¤ÁÕÃÐËÇèÒ§ÂÒ tetracycline ¡ÑºÊÒÃ·ÕèÁÕ»ÃÐ ØºÇ¡ (cation) àªè¹calcium, magnesium ËÃ×Í aluminum «Öè§¨Ð·ÓãËéà¡Ô cation-tetracycline complex ·ÓãËéÂÒ tetracycline äÁè¶Ù¡ Ù «ÖÁ¨Ò¡·Ò§à Ô¹ÍÒËÒÃ ÊèÇ¹ÂÒ cholestyramine ËÃ×Í colestipol ÊÒÁÒÃ¶ Ñº¡ÑºÂÒÍ×è¹·ÓãËé¡ÒÃ Ù «ÖÁÂÒÅ´Å§ àªè¹ meloxicam, warfarin

2. Interaction affecting oral bioavailability

2.1 Interaction affecting gastric emptying

ÂÒºÒ§ª¹Ô ÁÕ¼ÅµèÍÍÑµÃÒ¡ÒÃà¤Å×èÍ¹äËÇ¢Í§ÅÓäÊé (rate ofgastric emptying) â´Â¡ÒÃà»ÅÕèÂ¹á»Å§ÍÑµÃÒ¡ÒÃà¤Å×èÍ¹äËÇ¢Í§ÅÓäÊéÁÑ¡¨ÐäÁèÁÕ¼Åà»ÅÕèÂ¹á»Å§ªÕÇ»ÃÐÊÔ·¸Ô¼Å (bioavailability)áµè¨ÐÁÕ¼ÅµèÍàÇÅÒàÃÔèÁÍÍ¡Ä·¸Ôì¢Í§ÂÒ â´Âà©¾ÒÐÂÒ·ÕèµéÍ§¡ÒÃãËéÍÍ¡Ä· ÔìàÃçÇ (rapid onset) àªè¹ ÂÒá¡é»Ç´ËÃ×ÍÂÒ¹Í¹ËÅÑº »Ñ ÑÂ·Õ èÁ Õ¼Å·ÓãËé¡ÒÃà¤Å× èÍ¹äËÇ¢Í§ÅÓäÊéÅ´Å§ àªè¹ ÍÒËÒÃ ¡ÒÃÍÍ¡¡ÓÅÑ§¡ÒÂÍÂèÒ§Ë¹Ñ¡ ¡ÒÃ·Ó§Ò¹¢Í§ÃÐºº»ÃÐÊÒ·ÍÑµâ¹ÁÑµÔ¼Ô »¡µÔ (autonomic neuropathy) ËÃ×ÍÂÒã¹¡ÅØèÁ antacid, anti-cholinergic áÅÐ narcotics »Ñ ÑÂàËÅèÒ¹ÕéÁÑ¡¨ÐÁÕ¼Å·ÓãËé¡ÒÃ´Ù´«ÖÁÂÒªéÒÅ§ ÊèÇ¹ÂÒ·ÕèÁÕ¼Åà¾ÔèÁ¡ÒÃà¤Å×èÍ¹äËÇ¢Í§ÅÓäÊé àªè¹metoclopramide, cisapride, domperidone ÂÒ Ñ§¡ÅèÒÇ¨ÐÁÕ¼Å·ÓãËéàÇÅÒ·ÕèÃÐ´ÑºÂÒã¹àÅ×Í´¶Ö§¨Ø´ÊÙ§ÊØ´àÃçÇ¢Öé¹áÅÐÊÙ§¢Öé¹¡ÇèÒ»¡µÔËÒ¡µéÍ§¡ÒÃà¾ÔèÁÍÑµÃÒ¡ÒÃà¤Å×èÍ¹äËÇ¢Í§ÅÓäÊéã¹¢³Ð·Õè·éÍ§ÇèÒ§(empty stomach) à¾×èÍà¾ÔèÁ¡ÒÃ´Ù´«ÖÁÂÒ ·Óä´éâ´Â¡ÒÃãËé¼Ùé»èÇÂÃÑº»ÃÐ·Ò¹ÂÒ¾ÃéÍÁ¡Ñº¹éÓÍÂèÒ§¹éÍÂ 200 ÁÅ. áÅÐãËéÍÂÙèã¹·èÒ¹Ñè§(upright position)

ÍÂèÒ§äÃ¡çµÒÁ ÁÕÂÒºÒ§ÍÂèÒ§äÁèà»ç¹ä»µÒÁ¡®à¡³±ì´Ñ§¡ÅèÒÇàªè¹ ÂÒ·Õè¶Ù¡·ÓÅÒÂ éÇÂ¡Ã´ã¹¡ÃÐà¾ÒÐÍÒËÒÃàªè¹ penicillin ËÃ×Ílevodopa ¡ÒÃÅ´¡ÒÃà¤Å×èÍ¹äËÇ¢Í§ÅÓäÊé¡ÅÑº·ÓãËéÁÕ¡ÒÃ´Ù´«ÖÁÂÒÅ´Å§ ËÃ×Íã¹¡Ã³Õ·ÕèÂÒÁÕ¡ÒÃÅÐÅÒÂã¹ÅÓäÊéÍÂèÒ§ªéÒ æ àªè¹ ÂÒàÁç ·ÕèÍÂÙè

page P&D Information Bulletin / Vol. 13, No. 3, 2005 34

ã¹ÃÙ»¢Í§ enteric coated ¡ÒÃà¾ÔèÁ¡ÒÃà¤Å×èÍ¹äËÇ¢Í§ÅÓäÊé Ð·ÓãËé¡ÒÃ´Ù´«ÖÁÂÒ¨Ò¡·Ò§à´Ô¹ÍÒËÒÃÅ´Å§

2.2 Interaction affecting drug absorption

ÂÒÊèÇ¹ãËè Ð¶Ù¡ Ù «ÖÁ¼èÒ¹¼¹Ñ§ÅÓäÊéâ´ÂÇÔ Õ passive diffu-sion âÍ¡ÒÊà¡Ô DI ·ÕèÅ´¡ÒÃ Ù «ÖÁÂÒ¨Ò¡·Ò§à Ô¹ÍÒËÒÃ¤èÍ¹¢éÒ§¹éÍÂÁÕµÑÇÍÂèÒ§·ÕèÅ´¡ÒÃ Ù «ÖÁ¨Ò¡¡ÒÃà¡Ô DI ä éàªè¹ ¡ÒÃãËéÂÒ pheny-toin ·Ò§ÊÒÂÂÒ§ (nasogastric tube) â´Â¡ÒÃá¡Ðá¤»«ÙÅ¨Ð·ÓãËéÂÒÊèÇ¹Ë¹Öè§µÔ´ÊÒÂÂÒ§»ÃÔÁÒ³ÂÒ·Õè¶Ù¡´Ù´«ÖÁ¨Ò¡·Ò§à´Ô¹ÍÒËÒÃà¢éÒÊÙèã¹àÅ×Í´¨Ö§¹éÍÂÅ´Å§ ¹Í¡¨Ò¡¹ÕéÂÒ phenytoin ¨Ð¶Ù¡´Ù´«ÖÁÅ´Å§¶éÒãËé¾ÃéÍÁ¡ÑºÍÒËÒÃ·ÕèÃÑº»ÃÐ·Ò¹·ÑèÇä»ÃÇÁ·Ñé§ÍÒËÒÃã¹¡ÅØèÁ·Õèà»ç¹ enteral nutrition â´Â·ÓãËéÃÐ ÑºÂÒ phenytoin ã¹àÅ×Í´Å´Å§»ÃÐÁÒ³ 50-70 % ©Ð¹Ñé¹¨ÐµéÍ§àµÃÕÂÁÂÒã¹ÃÙ»áººÂÒ¹éÓá¢Ç¹-µÐ¡Í¹ à¾×èÍÅ´»ÃÔÁÒ³ÂÒ·ÕèµÔ´·Ò§ÊÒÂÂÒ§áÅÐÅéÒ§ÊÒÂÂÒ§ËÅÑ§¡ÒÃãËéÂÒ phenytoin ·Ø¡¤ÃÑé§ ¹Í¡¨Ò¡¹Õé¤ÇÃãËéÂÒËèÒ§¨Ò¡Á×éÍÍÒËÒÃÍÂèÒ§¹éÍÂ 2 ªÁ. áÅÐ¤ÇÃ¨ÐµÔ µÒÁÃÐ ÑºÂÒã¹àÅ×Í´ÍÂèÒ§ÊÁèÓàÊÁÍ

ÊÓËÃÑºÂÒ warfarin ÍÒËÒÃ·Õè¼Ùé»èÇÂÃÑº»ÃÐ·Ò¹â´Â·ÑèÇä»¨ÐäÁè¼ÅµèÍ¡ÒÃ´Ù´«ÖÁ¢Í§ÂÒ áµèÍÒËÒÃ·Õèà»ç¹ enteral nutrition¨ÐÁÕ¼Åã¹¡ÒÃÅ´¡ÒÃ´Ù´«ÖÁÂÒ warfarin ¨Ö§¤ÇÃãËéÂÒ warfarinãËéËèÒ§¨Ò¡ enteral nutrition ÍÂèÒ§¹éÍÂ 2 ªÁ.àªè¹à ÕÂÇ¡ÑºÂÒ pheny-toin ¹Í¡¨Ò¡¹Õé enteral nutrition ºÒ§ÍÂèÒ§¨ÐÁÕ»ÃÔÁÒ³¢Í§ vita-min K ¤èÍ¹¢éÒ§ÊÙ§ ËÒ¡¼Ùé»èÇÂä éÃÑº vitamin K ÁÒ¡à¡Ô¹¡ÇèÒ 140-500 Á¤¡./ÇÑ¹ ÍÒ¨ÁÕ¼Å·ÓãËé¡ÒÃÍÍ¡Ä· Ôì¢Í§ÂÒ warfarin Å´Å§

¡ÒÃà»ÅÕèÂ¹á»Å§ÀÒÇÐ¤ÇÒÁà»ç¹¡Ã´ã¹¡ÃÐà¾ÒÐÍÒËÒÃ´éÇÂÂÒÅ´¡Ã´ àªè¹ antacid, H

2-blocker, proton pump inhibitor

¨ÐÁÕ¼Å·ÓãËéÂÒ·Õè´Ù´«ÖÁä´é´Õ¨Ò¡ÀÒÇÐà»ç¹¡Ã´ã¹¡ÃÐà¾ÒÐÍÒËÒÃ¹Ñé¹¶Ù¡ Ù «ÖÁÅ´Å§ àªè¹ÂÒ indinavir, ketoconazole, itraconazole

3. Protein-binding interaction

àÁ×èÍÂÒà¢éÒÊÙè¡ÃÐáÊàÅ×Í´¨ÐÁÕ¡ÒÃ¡ÃÐ¨ÒÂµÑÇä»µÒÁÊèÇ¹µèÒ§æ¢Í§ÃèÒ§¡ÒÂ ¡ÒÃ¡ÃÐ¨ÒÂµÑÇ¢Í§ÂÒÁÒ¡ËÃ×Í¹éÍÂ¹Ñé¹¢Öé¹ÍÂÙè¡Ñº¡ÒÃà»ç¹â¤Ã§ÊÃéÒ§·ÕèÁÕ»ÃÐ Ø (ionic composition) ¤ÇÒÁÊÒÁÒÃ¶ã¹¡ÒÃÅÐÅÒÂã¹ä¢ÁÑ¹ ¡ÒÃ¨Ñº¡Ñºâ»ÃµÕ¹ (protein-binding) ¢Í§ÂÒ¹Ñé¹æ â´ÂµÑÇÂÒ·ÕèÍÍ¡Ä· Ôìà»ç¹ÂÒ·ÕèäÁè Ñº¡Ñºâ»ÃµÕ¹ (free drug,unbound form) ÂÒ·Õè Ñº¡Ñºâ»ÃµÕ¹ÊÙ§ àªè¹ phenytoin, warfarin,valproate ËÒ¡à¡Ô ¡ÒÃà»ÅÕèÂ¹á»Å§¢Í§ÃÐ Ñº albumin ã¹àÅ×Í´ËÃ×Íà¡Ô DI ¡ÑºÂÒ·ÕèáÂè§ Ñº¡Ñº albumin ¨Ð·ÓãËéà¡Ô ¡ÒÃà»ÅÕèÂ¹á»Å§¢Í§ÃÐ Ñº free drug ã¹àÅ×Í´ÍÂèÒ§ÁÒ¡ Â¡µÑÇÍÂèÒ§àªè¹ ÂÒ pheny-toin Ñº¡Ñº albumin »ÃÐÁÒ³ 90% Ö§ÁÕ free drug »ÃÐÁÒ³ 10%ËÒ¡ÁÕ¡ÒÃà»ÅÕèÂ¹á»Å§·ÓãËéÃÐ´Ñº albumin ã¹àÅ×Í´Å´Å§ËÃ×ÍÁÕ¡ÒÃáÂè§ Ñº¡Ñº albumin Ò¡ÂÒÍ×è¹ ÊÁØÁµÔÇèÒÁÕ¡ÒÃà¾ÔèÁ¢Öé¹¢Í§ freedrug à»ç¹ 15% ÐàËç¹ÇèÒ free drug à¾ÔèÁ¢Öé¹¨Ò¡à ÔÁ¶Ö§ 50% áµè¡ÒÃ

à¾ÔèÁ¢Öé¹¹Õéà»ç¹¡ÒÃà¾ÔèÁ¢Öé¹ªÑèÇ¤ÃÒÇ à¾ÃÒÐ¤ÇÒÁ¨ÃÔ§áÅéÇÂÒ·Õè¶Ù¡ metabo-lized ËÃ×Í¢ÑºÍÍ¡¡çÍÂÙèã¹ÃÙ»¢Í§ free drug áÅÐ¡ÒÃÁÕ distribution¢Í§ free drug ä»ÊÙè peripheral tissue ÁÒ¡¢Öé¹·ÓãËéÃÐ Ñº¢Í§ freedrug ¡ÅÑºà¢éÒÊÙèÀÒÇÐÊÁ´ØÅÂìÍÕ¡¤ÃÑé§â´Â¨ÐäÁèáµ¡µèÒ§¨Ò¡¡èÍ¹·Õè¨Ðà¡Ô DI ËÃ×Íà¡Ô ÀÒÇÐ albumin µèÓ áµèÃÐ ÑºÂÒ·ÕèÇÑ «Öè§ÍÂÙèã¹ÃÙ»¢Í§ total form ¨ÐÅ´Å§à¹×èÍ§¨Ò¡ bound form Å´Å§ Â¡µÑÇÍÂèÒ§àªè¹¡ÒÃãËé valproate ÃèÇÁ¡Ñº phenytoin (ÃÙ»·Õè 1)

¨ÐàËç¹ÇèÒÃÐ Ñº free drug ¢Í§ phenytoin äÁèà»ÅÕèÂ¹á»Å§ áµètotal concentration Å´Å§ÍÂèÒ§ªÑ à¨¹ ã¹¼Ùé»èÇÂ·ÕèÁÕ albumin µèÓÅ§¨Ò¡»¡µÔ free drug ¢Í§ phenytoin äÁèà»ÅÕèÂ¹á»Å§àªè¹¡Ñ¹ áµèÃÐ ÑºÂÒã¹àÅ×Í´·ÕèÇÑ ·Õèà»ç¹ total form ¨ÐµèÓ¡ÇèÒ»¡µÔ Ñ§ä éÍ ÔºÒÂä»áÅéÇ ã¹¼Ùé»èÇÂ·ÕèÁÕ albumin µèÓÊÒÁÒÃ¶¤Ó¹Ç³à¾×èÍ»ÃÑºËÒ¤èÒÃÐ ÑºÂÒ phenytoin ·Õè¤ÇÃ¨Ðà»ç¹¨Ò¡ÊÙµÃ Ñ§µèÍä»¹Õé

©Ð¹Ñé¹ ¡ÒÃà¨ÒÐÇÑ´ÃÐ´ÑºÂÒã¹àÅ×Í´ã¹ÀÒÇÐ´Ñ§¡ÅèÒÇ´éÇÂ¡ÒÃµÃÇ¨ÇÑ ÃÐ Ñº free drug ÐªèÇÂã¹¡ÒÃá»Å¼Åä é¶Ù¡µéÍ§áÁè¹ÂÓÁÒ¡¡ÇèÒ

4. Interaction due to altered biotransformation

¢ºÇ¹¡ÒÃ metabolism ¢Í§ÂÒã¹ÃèÒ§¡ÒÂÁÕ¤ÇÒÁáµ¡µèÒ§ÃÐËÇèÒ§ºØ¤¤Å¤èÍ¹¢éÒ§ÁÒ¡áÅÐÁÕ¼Å¡ÃÐ·ºÁÒ¡¨Ò¡¡ÒÃà¡Ô´ DI©Ð¹Ñé¹ ¡ÒÃà¡Ô´ DI «Öè§ÁÕ¼ÅµèÍ¡ÒÃ metabolism ¨Ö§ÁÕ¤ÇÒÁÊÓ¤ÑáÅÐÁÕ¡ÒÃÈÖ¡ÉÒÇÔ¨ÑÂÍÂèÒ§¡ÇéÒ§¢ÇÒ§ ·ÓãËé¡ÒÃÍ¸ÔºÒÂ¡ÒÃà¡Ô´ DI

ÃÙ»·Õè 1 áÊ´§ÃÐ Ñº¢Í§ phenytoin total concentration,free drug áÅÐ %free drug ÃÐËÇèÒ§·Õèä éÃÑº ÂÒ valproate

Phenytoin conc = Observed concentration (mg/L) (mg/L) 0.2 X serum albumin (g/(dL) +0.1

OD à·èÒ¹Ñé¹ ÂÒ·ÕèÁÕÄ·¸Ôì¡ÃÐµØé¹¹Ñé¹ÍÒ¨¡ÃÐµØé¹¡ÒÃ metabolism¢Í§µ¹àÍ§ (autoinduction) àªè¹ carbamazepine Ðà¡Ô autoin-duction ã¹ªèÇ§ 2 ÊÑ»´ÒËìàáÃ¡·ÕèãªéÂÒ ¡ÒÃµÃÇ¨ÇÑ ÃÐ ÑºÂÒã¹àÅ×Í´ã¹ÃÐÂÐ Ñ§¡ÅèÒÇ¨Ðá»Å¼ÅÂÒ¡

â´Â·ÑèÇä»¡ÒÃ¡ÃÐµØé¹¡ÒÃ metabolism ÁÕ¼Åà¾ÔèÁ clearance¢Í§ OD ¨Ð·ÓãËéÃÐ´ÑºÂÒã¹àÅ×Í´¢Í§ OD Å´Å§ ·ÓãËé¡ÒÃÍÍ¡Ä· Ôì¢Í§ÂÒ Ñ§¡ÅèÒÇÅ´Å§ éÇÂËÒ¡ OD à»ç¹µÑÇÂÒÍÍ¡Ä· Ôì äÁèãªèmetabolite ã¹·Ò§µÃ§¡Ñ¹¢éÒÁËÒ¡ metabolite à»ç¹µÑÇÍÍ¡Ä· Ôì¡ç Ð·ÓãËéà¡Ô ¾ÔÉÁÒ¡¢Öé¹ áµèâ´ÂÊèÇ¹ãËèÁÑ¡à»ç¹¡Ã³ÕáÃ¡ÁÒ¡¡ÇèÒ¢ÍÂ¡µÑÇÍÂèÒ§¡ÒÃà¡Ô induction ·ÕèÊÓ¤Ñ àªè¹ ¡ÒÃãªéÂÒ phenytoinã¹¡ÒÃ»éÍ§¡Ñ¹ªÑ¡ ã¹¼Ùé»èÇÂâÃ¤ÅÁªÑ¡à¾ÈËÔ§·ÕèÍÂÙèã¹ÇÑÂà¨ÃÔ¾Ñ¹¸Øì¨ÐäÁèá¹Ð¹ÓãËéãªé combined pill ã¹¡ÒÃ¤ØÁ¡Óà¹Ô à¹×èÍ§¨Ò¡ pheny-toin à»ç¹ inducer ¢Í§ CYP3A4 ·Õè·ÓË¹éÒ·Õèã¹¡ÒÃ metabolizedÎÍÃìâÁ¹ estrogen áÅÐ progesterone ·Õèà»ç¹ÊèÇ¹»ÃÐ¡Íºã¹ com-bined pill ·ÓãËéÃÐ Ñº¢Í§ÎÍÃìâÁ¹·Ñé§ 2 µÑÇÅ´Å§¨¹ÍÒ¨äÁèÁÕÄ· Ôìà¾ÕÂ§¾Íã¹¡ÒÃ¤ØÁ¡Óà¹Ô ä é ËÃ×Íã¹¡Ã³Õ·Õè¼Ùé»èÇÂ COPD ·ÕèÁÕ»ÃÐÇÑµÔÊÙººØËÃÕèà»ç¹»ÃÐ¨Ó àÁ×èÍä éÃÑº¡ÒÃÃÑ¡ÉÒ éÇÂ theophylline ¨Ð¾ºÇèÒÃÐ´ÑºÂÒã¹àÅ×Í´ÍÒ¨¨ÐµèÓ¡ÇèÒ»¡µÔ à¹×èÍ§¨Ò¡ÊÒÃã¹ºØËÃÕè¨ÐÍÍ¡Ä·¸Ôì¡ÃÐµØé¹¡ÒÃ·Ó§Ò¹¢Í§ CYP1A2 ·Õè·ÓË¹éÒ·Õèã¹¡ÒÃ metabolized ÂÒtheophylline ·ÓãËéÃÐ ÑºÂÒ theophylline ã¹àÅ×Í´Å´Å§ Ö§¤Çº¤ØÁÍÒ¡ÒÃËÍºË×´äÁèä´é

ã¹ºÒ§¡Ã³Õ¡ÒÃà¡Ô´¡ÒÃ¡ÃÐµØé¹¡ÒÃ·Ó§Ò¹¢Í§àÍç¹ä«Áìã¹¡ÒÃmetabolism ¢Í§ÂÒÍÒ¨·ÓãËéà¡Ô toxic metabolite à¾ÔèÁ¢Öé¹ àªè¹ËÒ¡¼Ùé»èÇÂ·Õèä éÃÑº isoniazid à¾×èÍÃÑ¡ÉÒÇÑ³âÃ¤ÍÂÙèáÅéÇÃÑº»ÃÐ·Ò¹ÂÒparacetamol à¡Ô¹¢¹Ò´ ÍÒ¨¨Ð·ÓãËé¼Ùé»èÇÂÃÒÂ¹ÕéÁÕâÍ¡ÒÊà¡Ô ¾ÔÉ¨Ò¡paracetamol ÁÒ¡¡ÇèÒ»¡µÔ à¹×èÍ§¨Ò¡ paracetamol ÊèÇ¹Ë¹Öè§¨Ð¶Ù¡metabolized ¼èÒ¹ CYP2E1 ä é toxic metabolite ¤×Í N-acetyl-p-benzoquinonemine (NAPQI) «Öè§ÁÕÄ· Ôì·ÓãËéà¡Ô µÑºÍÑ¡àÊºisoniazid ÁÕÄ· Ôì¡ÃÐµØé¹¡ÒÃ·Ó§Ò¹¢Í§ CYP2E1 ·ÓãËéä é NAPQIÁÒ¡¢Öé¹ Ö§·ÓãËéÁÕâÍ¡ÒÊà¡Ô ¾ÔÉÁÒ¡¢Öé¹

5. Interaction due to altered renal excretion

ÂÒ·ÕèÊÒÁÒÃ¶ÅÐÅÒÂ¹éÓä´é´Õ ¨Ð¶Ù¡¢ÑºÍÍ¡¨Ò¡ÃèÒ§¡ÒÂ·Ò§äµ¡ÒÃ¢ÑºÂÒÍÍ¡¨Ò¡ÃèÒ§¡ÒÂâ´Â¢ºÇ¹¡ÒÃ glomerular filtration ¹Ñé¹äÁèä´éÃÑº¼Å¡ÃÐ·º¨Ò¡ÂÒÍ×è¹ «Öè§áµ¡µèÒ§¨Ò¡¢ºÇ¹¡ÒÃ tubularsecretion ¹Ñé¹ÍÒ¨¨Ðä éÃÑº¼Å¡ÃÐ·º¨Ò¡ÂÒÍ×è¹ä é Â¡µÑÇÍÂèÒ§àªè¹ ÂÒprobenecid ÐÅ´ clearance ¢Í§ penicillin ·Õèäµ ·ÓãËéÃÐÂÐàÇÅÒ¡ÒÃÍÍ¡Ä· Ôì¢Í§ÂÒ penicillin ÂÒÇ¹Ò¹ÁÒ¡¢Öé¹ ·ÓãËé¼Å¡ÒÃÃÑ¡ÉÒ¢Í§penicillin Õ¢Öé¹ ËÃ×Íã¹·Ò§µÃ§¡Ñ¹¢éÒÁ ÂÒ salicylate ¨Ðä»ÂÑºÂÑé§¡ÒÃ¢ÑºÍÍ¡¢Í§ÂÒ methotrexate ·ÓãËé¼Ùé»èÇÂ·Õèä éÃÑºÂÒ·Ñé§ÊÍ§ÃèÇÁ¡Ñ¹à¡Ô ¾ÔÉ¨Ò¡ÂÒ methotrexate ä é

ã¹¡Åä¡·Õè¼èÒ¹¢ºÇ¹¡ÒÃ metabolism ¹Ñé¹ÊÒÁÒÃ¶Í¸ÔºÒÂä´éÍÂèÒ§ªÑ à¨¹ÁÒ¡¢Öé¹ã¹»Ñ ØºÑ¹ â´Âà©¾ÒÐ¼èÒ¹àÍç¹ä«Áì cytochrome P450(CYPs) â´Â¾ºÇèÒÂÒ·Õè¶Ù¡ metabolism ¼èÒ¹µÑº»ÃÐÁÒ³ 50% ¶Ù¡metabolism ¼èÒ¹àÍç¹ä«Áìã¹¡ÅØèÁ¢Í§ CYPs CYPs ·Õèà¡ÕèÂÇ¢éÍ§¡Ñº¡ÒÃ metabolism ÂÒ ÊÒÃà¤ÁÕËÃ×ÍÍÒËÒÃã¹ÃèÒ§¡ÒÂ¹Ñé¹»ÃÐ¡Íº éÇÂCYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1áÅÐ CYP3A4 â´ÂÂÒ ÊÒÃà¤ÁÕ ËÃ×Í ÍÒËÒÃ·Õè¶Ù¡ metabolism ¼èÒ¹¡ÅØèÁ¢Í§àÍç¹ä«ÁìàËÅèÒ¹ÕéàÃÕÂ¡ÇèÒ substrate àªè¹ ÂÒã¹¡ÅØèÁ macrolideàªè¹ erythromycin, roxithromycin (Â¡àÇé¹ azithromycin) à»ç¹substrate ¢Í§ CYP3A4 (ÃÒÂÃÐàÍÕÂ´áÊ´§äÇéã¹Ë¹éÒ 32)

4.1 interaction involving enzyme inhibition

ÂÒ·Õè¼Ù é»èÇÂä´éÃÑºã¹»Ñ¨¨ØºÑ¹¾ºÇèÒÁÕÄ·¸ÔìÂÑºÂÑ é§¡ÒÃ·Ó§Ò¹¢Í§àÍç¹ä«Áì·Õè metabolized ÂÒÍ×è¹ â´ÂÄ· ÔìÂÑºÂÑé§¹Õé ÐÁÕ¼Å·ÓãËéclearance ¢Í§ OD Å´Å§ ·ÓãËéÃÐ Ñº OD ã¹àÅ×Í´à¾ÔèÁ¢Öé¹ áÅÐmetabolite ¢Í§ OD Å´Å§ àÁ×èÍà¢éÒÊÙè steady state ãËÁè ã¹¡Ã³Õ·ÕèOD à»ç¹µÑÇÍÍ¡Ä·¸Ôì¨Ð·ÓãËéÁÕâÍ¡ÒÊ·Õè¨Ðà¡Ô´¼Å¢éÒ§à¤ÕÂ§¨Ò¡ÂÒà¾ÔèÁ¢Öé¹ áµèã¹·Ò§µÃ§¡Ñ¹¢éÒÁËÒ¡ metabolite ¢Í§ OD à»ç¹µÑÇÍÍ¡Ä·¸Ôì¨ÐÁÕ¼Å·ÓãËé¡ÒÃÍÍ¡Ä·¸Ôì¢Í§ÂÒÅ´Å§ áµèâ´ÂÊèÇ¹ãËèáÅéÇÁÑ¡¨Ðà»ç¹ inactive metabolite ÂÒ·ÕèÁÕÄ· ÔìÂÑºÂÑé§¡ÒÃ·Ó§Ò¹¢Í§CYPs ä éáÊ´§äÇéã¹Ë¹éÒ 30-32

¹Í¡¨Ò¡¡ÒÃÍÍ¡Ä·¸ÔìÂÑºÂÑé§¡ÒÃ metabolism â´ÂµÃ§áÅéÇÂÒ·Õè¶Ù¡ metabolized éÇÂàÍç¹ä«ÁìµÑÇà ÕÂÇ¡Ñ¹¨Ð·ÓãËéà¡Ô ¡ÒÃáÂè§metabolized ¼èÒ¹àÍç¹ä«ÁìµÑÇà ÕÂÇ¡Ñ¹ä é ÍÒ¨·ÓãËéÃÐ ÑºÂÒã¹àÅ×Í´¢Í§ÂÒ·Ñé§ 2 µÑÇà¾ÔèÁ¢Öé¹ä é Â¡µÑÇÍÂèÒ§àªè¹ warfarin ¡Ñº phenytoin·Õè¶Ù¡ metabolized ËÅÑ¡¼èÒ¹ CYP2C9 àËÁ×Í¹¡Ñ¹ ËÒ¡ãËéÂÒ·Ñé§ 2ÃèÇÁ¡Ñ¹µéÍ§à½éÒÊÑ§à¡µÍÒ¡ÒÃ¢éÒ§à¤ÕÂ§¢Í§ÂÒ·Ñé§ÊÍ§ËÃ×ÍÇÑ´ÃÐ´ÑºÂÒã¹àÅ×Í´ (therapeutic drug monitoring) à»ç¹ÃÐÂÐ

ÃÐÂÐàÇÅÒ¢Í§¡ÒÃà»ÅÕèÂ¹á»Å§ÃÐ ÑºÂÒã¹àÅ×Í´¢Í§ OD ¹Ñé¹¢Öé¹ÍÂÙè¡Ñº¤èÒ¤ÃÖè§ªÕÇÔµãËÁè¢Í§ OD ËÅÑ§à¡Ô´¡ÒÃÂÑºÂÑé§¡ÒÃ·Ó§Ò¹¢Í§àÍç¹ä«Áì

4.2 interaction involving enzyme induction

àÍç¹ä«Áì·Õè·ÓË¹éÒ metabolism ÂÒ ËÃ×ÍÊÒÃà¤ÁÕÊÒÁÒÃ¶¶Ù¡¡ÃÐµØé¹¡ÒÃ·Ó§Ò¹ (induction) ä´éâ´ÂÂÒ ÊÒÃà¤ÁÕ ÍÒËÒÃ ËÃ×ÍÊÁØ¹ä¾ÃÍ×è¹ ¡Åä¡¡ÒÃ¡ÃÐµØé¹ÁÕËÅÒÂáººáµèâ´Â·ÑèÇæ ä»¨Ðà»ç¹¡ÒÃà¾ÔèÁ»ÃÔÁÒ³¢Í§àÍç¹ä«Áì ·ÓãËéà¾ÔèÁ Vmax ÃÐÂÐ¢Í§àÇÅÒ¢Í§¡ÒÃà¡Ô´¡ÒÃ¡ÃÐµØé¹¹Ñé¹¨ÐãªéàÇÅÒ¹Ò¹¡ÇèÒ¡ÒÃÂÑºÂÑé§ â´ÂãªéàÇÅÒ»ÃÐÁÒ³ 2- 3 ÊÑ»´ÒËìà¾×èÍãËéàËç¹¼ÅÊÙ§ÊØ â´ÂÂÒ·ÕèÍÍ¡Ä· Ôìã¹¡ÒÃ¡ÃÐµØé¹¡ÒÃ·Ó§Ò¹¢Í§ CYPs ·Õèà¡ÕèÂÇ¢éÍ§¡Ñº¡ÒÃ metabolism áÊ´§äÇéã¹Ë¹éÒ 30-32

¡ÒÃ¡ÃÐµØé¹¢ºÇ¹¡ÒÃ metabolism àÍ§äÁèä éà¡Ô ¢Öé¹à©¾ÒÐ¡Ñº


¡Ã³Õ·ÕèÁÕâÍ¡ÒÊàÊÕèÂ§µèÍ¡ÒÃà¡Ô DI ÊÙ§¢Öé¹ (High risk clinical set-ting)

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¤ÇÃà½éÒÃÐÁÑ ÃÐÇÑ§à»ç¹¾ÔàÈÉ àªè¹

1. ¼Ùé»èÇÂä éÃÑºÂÒ·ÕèÁÕ therapeutic index á¤º àªè¹ warfarin,

phenytoin, cyclosporine, digoxin, lithium, theophylline

2. ¼Ù é»èÇÂ·Õ èä´éÃ ÑºÂÒËÅÒÂ æ ª¹Ô´ÃèÇÁ¡Ñ¹â´Âà©¾ÒÐÂÒ

·Õè¼Ùé»èÇÂ«×éÍàÍ§â´ÂäÁèÁÕãºÊÑè§á¾·Âì ËÃ×ÍÂÒÊÁØ¹ä¾Ã

3. ¼Ùé»èÇÂã¹ÀÒÇÐÇÔ¡ÄµÔ ¼Ùé»èÇÂ¡ÅØèÁ¹ÕéÁÑ¡ÁÕ¡ÒÃãªéÂÒËÅÒÂæ ª¹Ô

ÃèÇÁ¡Ñ¹áÅÐÁÑ¡ÁÕâÃ¤·ÕèÁÕ¡ÒÃà»ÅÕèÂ¹á»Å§¡ÒÃ metabolism ¢Í§ÂÒ

ã¹ÃèÒ§¡ÒÂ àªè¹ ÁÕ¡ÒÃ·Ó§Ò¹¢Í§µÑºËÃ×Íäµ·ÕèáÂèÅ§

4. ¼Ùé»èÇÂàÍ´Êì ¨Ò¡¡ÒÃÈÖ¡ÉÒ¾ºÇèÒ¼Ùé»èÇÂ¡ÅØèÁ¹ÕéÁÕâÍ¡ÒÊÊÙ§

·Õè ÐÁÕ¡ÒÃ·Ó§Ò¹¢Í§ÍÇÑÂÐµèÒ§ æ Å´Å§ à¹×èÍ§¨Ò¡ÀÒÇÐµÔ àª×éÍ«Öè§¨ÐÁÕ

¼ÅµèÍ¡ÒÃà»ÅÕèÂ¹á»Å§ÂÒã¹ÃèÒ§¡ÒÂ áÅÐ¾ºÇèÒÁÑ¡¨Ðà¡Ô´ÀÒÇÐ¼×è¹

á¾éÂÒÊÙ§¡ÇèÒ»ÃÐªÒ¡Ã·ÑèÇæä» ÃèÇÁ¡Ñº¡ÒÃãªéÂÒËÅÒÂæ ÍÂèÒ§ÃèÇÁ¡Ñ¹

·ÕèÁÕ¼Å¢éÒ§à¤ÕÂ§·ÕèÃØ¹áÃ§

5. ¼Ùé»èÇÂÊÙ§ÍÒÂØ áÅÐ¼Ùé»èÇÂ ÔµàÇª

ÊÃØ»àÁ×èÍÁÕ¡ÒÃÊÑè§¨èÒÂãËé¼Ùé»èÇÂÁÒ¡¡ÇèÒËÃ×Íà·èÒ¡Ñº 2 ª¹Ô´¢Öé¹ä»

á¾·ÂìËÃ×ÍàÀÊÑª¡Ã¤ÇÃ¨ÐµÃÐË¹Ñ¡¶Ö§ÀÒÇÐ DI äÇéàÊÁÍ áÅÐ

¾Ô ÒÃ³ÒÇèÒÂÒ·ÕèÊÑè§ èÒÂãËé¹Ñé¹ÁÕâÍ¡ÒÊà¡Ô DI ËÃ×ÍäÁè ËÒ¡¡ÒÃà¡Ô

DI ¹Ñé¹ÁÕÃÒÂ§Ò¹ÇèÒÁÕ¤ÇÒÁÊÓ¤Ñ·Ò§¤ÅÔ¹Ô¡¤ÇÃàÅÕèÂ§ãªéÂÒÍ×è¹·ÕèäÁè

à¡Ô´ DI á·¹ ËÃ×Í¤ÇÃà½éÒÃÐÇÑ§¼Å¢éÒ§à¤ÕÂ§·Õèà¡Ô´¢Öé¹ÍÂèÒ§ã¡ÅéªÔ´

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pharmacokinetic ¤ÇÃ¨Ð»ÃÐàÁÔ¹ÇèÒÁÕ¼Å¡ÃÐ·ºµèÍ absorption,

distribution, metabolism áÅÐ elimination (ADME) ËÃ×ÍäÁè

«Öè§¨ÐªèÇÂãËéËÒÊÒàËµØä é§èÒÂáÅÐ¤Ãº¶éÇ¹ÂÔè§¢Öé¹ ·ÓãËéÊÒÁÒÃ¶á¡éä¢

¼Å¢éÒ§à¤ÕÂ§¹Ñé¹ä éÍÂèÒ§¶Ù¡µéÍ§ ¶Ö§áÁé¡ÒÃà¡Ô DI ºÒ§¤ÃÑé§ÍÒ¨äÁèÁÕ

¤ÇÒÁÊÓ¤Ñ·Ò§¤ÅÔ¹Ô¡áµè¤ÇÃ¨ÐÃÐÁÑ´ÃÐÇÑ§ã¹¡Ã³Õ·Õè¼Ùé»èÇÂÍÂÙèã¹

¡ÅØèÁàÊÕèÂ§ àªè¹ ä éÃÑºÂÒËÅÒÂª¹Ô ÃèÇÁ¡Ñºä éÃÑºÂÒ·ÕèÁÕ therapeutic

index á¤º à»ç¹µé¹

àÍ¡ÊÒÃ»ÃÐ¡Íº¡ÒÃàÃÕÂºàÃÕÂ§1. Anderson GD. A Mechanistic approach to antiepileptic

drug interactions. Ann Pharmacother 1997; 32:554-62.

2. Tanaka E. Clinically important pharmacokinetic drug- drug

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