INTERACTIONS AMONG PRIMAQUINE, MALARIA INFECTION AND OTHER ANTIMALARIALS IN THAI SUBJECTS

1 The pharmacokinetics of rac-primaquine (45 mg base) and its principal plasma metabolite, carboxyprimaquine have been investigated in healthy Thai adults prior to and following a single oral dose of mefloquine (10 mg kg-1). 2 Primaquine was rapidly absorbed, attaining peak plasma concentrations (median and range) of 167 (113-532) mug l-1 in 2 (1-4) h. Thereafter, concentrations declined rapidly with an apparent terminal half-life of 6.1 (1.7-16.1) h and an oral clearance (CLpo) of 33.1 (17.6-49.3) l h-1. Administration of mefloquine had no effect on the values of any of these parameters at the 5% level of significance [C(max) 229 (114-503) mug l-1; (t)max 3 (2-4) h; t1/2,Z 3.9 (1.7-13.5) h; CLpo 34.0 (21.7-49. 0) l h-1]. 3 The carboxylic acid metabolite of primaquine achieved maximum concentrations (median and range) of 890 (553-3634) mug l-1 at 6 (3-16) h. Thereafter, plasma concentrations of carboxyprimaquine declined to 346 (99-918) mug l-1 at 24 h. AUC (0,24 h) was 12737 (6837-27388) mug l-1 h. Administration of mefloquine had no effect on the plasma concentrations of this metabolite [C(max) 1035 (174-3015) mug l-1; t(max) 8 (2-24) h; AUC(0,24) 13471 (2132-17863) mug l-1 h]. 4 The effect of falciparum malaria and treatment with quinine (10 mg salt kg-1 p.o.) on the pharmacokinetics of primaquine (45 mg base p.o.) has been investigated in adult Thai patients during and after infection with falciparum malaria. Acute falciparum malaria was associated with a statistically significant (P < 0.05) reduction in oral clearance (l h-1; median and range) of primaquine from 21.3 (15.9-73.0) to 19.4 (9.3-24.7). 5 The area under the curve (AUC(O, 24 h); mug l-1 h) for the carboxylic acid metabolite of primaquine (median and range) was significantly greater (P < 0.05) following the administration of primaquine alone (7533; 4876-18545) relative to the combination of quinine and primaquine (3831; 2144;5882).