Oral absorption and presystemic first-pass effect of chlorpheniramine in rabbits.

The oral absolute bioavailabilities of chloropheniramine (CPM) in four rabbits (New Zealand White, male, mean wt. 3.71 kg), averaged 0.06 +/- 0.03, 0.11 +/- 0.08, and 0.09 +/- 0.01 following a 3, 10.5, and 21 mg/kg dose, respectively. The individual bioavailability data and the AUC of one of the demethylated metabolites, desdimethyl CPM (DDCPM) obtained following different doses suggested the existence of saturable presystemic elimination. Two rabbits received an additional 10.5 mg/kg dose of CPM through portal vein infusion. Based on the oral, intraportal vein and i.v. studies, the mean extraction ratios of gut and the liver calculated for these two rabbits averaged 0.58 and 0.76, respectively. The latter value agreed well with the estimated hepatic extraction ratio from the in vitro liver homogenate study (0.89) or from the i.v. studies (0.83). The existence prehepatic first-pass effect observed in the present study was consistent with similar findings in humans and dogs.