Arterial and venous blood sampling in pharmacokinetic studies: griseofulvin

The pharmacokinetics of griseofulvin were evaluated simultaneously using both arterial and venous plasma in three dogs and one rabbit after a rapid bolus intravenous dosing. Initial arterial-venous ratios 20 sec after injection were the highest and ranged from 15- to 752-fold for dogs; the ratio was 3240-fold for the rabbit. Both curves decayed paralleling each other at the terminal phase with the venous levels higher than arterial levels by 14-43 and 8.4% for the dogs and the rabbit, respectively. The use of the instantaneous input principle was found to overestimate the total area under the plasma level-time curve by as much as 166%. An exponential term with a negative coefficient was used to account for the short and steep rising phase of plasma levels after injection. Detailed analyses showed significant differences in various calculated pharmacokinetic parameters based on arterial or venous data. The present study exemplifies the need for careful assessment and interpretation of classical pharmacokinetic parameters. It appeared that short intravenous infusion rather than the instantaneous or rapid bolus intravenous injection should be preferred for routine pharmacokinetic studies.