HEPARIN CAN DEGRADE PLASMA TRIGLYCERIDES IN BLOOD SAMPLES IN VITRO

And may alter the apparent protein binding of phenytoin and prazosinThe administration of heparin causes release of lipases into the bloodstream, resulting in the breakdown of plasmatriglycerides to non-esterified (free) fatty acids. High levels of free fatty acids have been reported in patients onheparin, but this may be an artifact, since degradation of triglycerides continues to take place in vitro after bloodsampling.The effects of low IV doses of heparin (I, 10, 20 and 30 U/kg) on the concentration of free fatty acids in vivo and invitro, and on the protein binding of phenytoin and prazosin, were evaluated in 4 healthy men aged 20-25 years. Eachsubject received the 4 doses of heparin in crossover fashion on 4 different days.There were transient increases in free fatty acids in vivo (5,8 and 15 min after heparin 10,20 and 30 U/kg), but thesewere less than 0.2 mEq/L. However, free fatty acid levels increased markedly in vitro (when samples were taken in theabsence of a lipase inhibitor) 8 min after all 4 doses of heparin. There seemed to be few consistent changes in theplasma binding of either phenytoin or prazosin, although, following the 20 and 30 U/kg doses of heparin, the increasesin free fatty acids were accompanied by increased levels of free phenytoin and prazosin. This produced only smallchanges in the phenytoin and prazosin ratios of plasma to whole blood concentrations. Pre-heparin concentrations oftriglycerides ranged between 0.166-1.14 giL, but free fatty acid concentrations following in vitro incubation of post­heparin plasma (without a lipase inhibitor) were significantly correlated with baseline triglyceride only after the20 UIkg dose.'The observation that administration of a small dose of heparin will modify the binding of phenytoin and prazosinunless appropriate precautions to inhibit in vitro lipolysis are taken is pertinent to pharmacokinetic studies in normalsubjects and to routine drug monitoring in patients'.Schulz. P. el al.: European Journal of Clinical Pharmacology 25: 211 (No 2, 1983)

0156-2703/83/1112-0015/0$01.00/0 © ADIS Press INPHARMA 12 Nov 1983 15