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Abstract

Effect of blood sampling schedules on protein drug binding in the rat.

M Hulse, S Feldman and J V Bruckner
Journal of Pharmacology and Experimental Therapeutics August 1981, 218 (2) 416-420;
M Hulse
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S Feldman
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J V Bruckner
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Abstract

The effect of repetitive blood sampling schedules on the plasma protein binding of a highly protein-bound drug, dicumarol, was investigated in the rat. Blood samples were withdrawn at pre-determined intervals and hematocrit, total plasma protein, plasma albumin and free fatty acids were measured. Plasma protein binding of [14C]dicumarol was assessed by equilibrium dialysis. Withdrawal of 1 ml of blood every hour for 12 hr produced a significant decrease at 2 hr in hematocrit (42%), total plasma protein (14.5%), plasma albumin (31.4%) and an increase in free fatty acids (238%) compared to the control (O time) levels. The free fraction of dicumarol in the plasma increased 1350%, from 0.38 to 5.13%. Sampling schedules involving blood withdrawal of 0.5 mg/2 hr and 1 ml/2 hr producing less dramatic changes, but in all cases the free fraction of dicumarol was elevated at the 12-hr time period. An inverse relationship was found between plasma albumin concentrations and dicumarol-free fraction. The blood sampling schedule was found to alter the pharmacological response (prothrombin time) and pharmacokinetics of dicumarol after an 8 mg/kg i.v. dose. These results illustrate the influence multiple blood sampling can exert on pharmacodynamic parameters in studies involving small laboratory animals and highly protein-bound drugs.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 218, Issue 2
1 Aug 1981
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Abstract

Effect of blood sampling schedules on protein drug binding in the rat.

M Hulse, S Feldman and J V Bruckner
Journal of Pharmacology and Experimental Therapeutics August 1, 1981, 218 (2) 416-420;

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Abstract

Effect of blood sampling schedules on protein drug binding in the rat.

M Hulse, S Feldman and J V Bruckner
Journal of Pharmacology and Experimental Therapeutics August 1, 1981, 218 (2) 416-420;
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