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

Abstract

1 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 ,uCi), simultaneously with the 45 mg oral dose. 2 Absorption of primaquine was virtually complete with a mean absolute bioavailability of 0.96 ± 0.08. 3 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. 4 The relationships between area under the curve and dose size were linear for both primaquine (r = 0.99, P -0.01) and its carboxylic acid metabolite (r = 0.99, P , 0.01). 5 The mean whole blood to plasma concentration ratios were determined for primaquine (0.81), and for the carboxylic acid metabolite of primaquine (0.84). 6 Primaquine is a low clearance compound (CL = 24.2 ± 7.4 1 h-1), is extensively distributed into body tissues (V = 242.9 ± 69.51) and is not subject to extensive first pass metabolism.

Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects.

“…There were no significant differences in the pharmacokinetic parameters of primaquine determined in the Thai subjects in this study (Table 1) compared to those derived from Caucasians (Mihaly et al, 1985a). This implies that data from studies undertaken in European volunteers can be extrapolated readily to those individuals who are more at risk of contracting malaria.…”

“…In the preceding publication (Mihaly et al, 1985a), we reported primaquine to be completely bioavailable and that its disposition was not influenced by increasing dose size (15 to 45 mg). A definitive study of the effect of chronic dosage on the pharmacokinetics of primaquine has not been performed.…”

“…Chemicals, chromatography and assay methods All reagents, chemicals and chromatography equipment were identical to those described previously (Mihaly et al, 1985a). Similarly, assay methods for primaquine and its carboxylic acid metabolite utilized sensitive and selective hplc methods described in detail elsewhere Mihaly et al, 1984).…”

“…The pharmacokinetic parameters, peak plasma drug concentrations (Cmax), the time at which they were reached (tmax), terminal phase elimination rate constant (X,), terminal phase elimination half-life (t½,) and the area under the curve from time 0 to infinity (AUC) and oral clearance (CLO) were all calculated as described previously (Mihaly et al, 1985a (Figure la). This is reflected in the almost identical values obtained for the mean pharmacokinetic parameters for primaquine calculated after acute and chronic dose studies (Table 1).…”

“…method for the measurement of primaquine has enabled detailed investigations of single dose pharmacokinetics to be carried out in man (Mihaly et al, 1984(Mihaly et al, , 1985a. We have examined the effect of dose size (across the therapeutic range from 15 to 45 mg) and the influence of route of administration on the pharmacokinetics of both parent drug and its carboxylic acid metabolite (Mihaly et al, 1985a).…”