Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size.

The pharmacokinetics of primaquine have been examined in five healthy volunteers who received single oral doses of 15, 30 and 45 mg of the drug, on separate occasions. Each subject received an i.v. tracer dose of [14C]-primaquine (7.5 microCi), simultaneously with the 45 mg oral dose. Absorption of primaquine was virtually complete with a mean absolute bioavailability of 0.96 +/- 0.08. Elimination half-life, oral clearance and apparent volume of distribution for both primaquine and the carboxylic acid metabolite were unaffected by either dose size, or route of administration. The relationships between area under the curve and dose size were linear for both primaquine (r = 0.99, P less than or equal to 0.01) and its carboxylic acid metabolite (r = 0.99, p less than or equal to 0.01). The mean whole blood to plasma concentration ratios were determined for primaquine (0.81), and for the carboxylic acid metabolite of primaquine (0.84). Primaquine is a low clearance compound (CL = 24.2 +/- 7.4 l h-1), is extensively distributed into body tissues (V = 242.9 +/- 69.5 l) and is not subject to extensive first pass metabolism.