Marked enhancement by rifampicin and lack of effect of isoniazid on the elimination of quinine in man.
The effect of rifampicin and isoniazid pretreatment on the pharmacokinetics of quinine after a single oral dose (600 mg quinine sulphate) was studied in nine healthy young Thai male volunteers using a three-way randomized crossover design. Subjects were studied over three 2 day periods, during which they received no pretreatment, or pretreatment with daily 600 mg p.o. rifampicin for 2 weeks, or isoniazid 300 mg p.o. daily for 1 week, prior to quinine administration. The mean (+/- s.d.) clearance (CL/F) of quinine coadministered with rifampicin (0.87 +/- 0.35 1 h-1 kg-1) was significantly greater than that of quinine alone (0.14 +/- 0.05 1 h-1 kg-1). The mean difference in clearance from the control treatment was 0.73 1 h-1 kg-1, with 95% confidence interval (C.I.) of 0.48 to 0.98. The unbound clearance (CLu/F) of quinine, which reflects the activity of the drug-metabolizing enzymes, was considerably greater (6.9-fold) in subjects when rifampicin was coadministered with quinine than that of quinine alone (6.9 +/- 3.6 vs 1.0 +/- 0.5 1 h-1 kg-1; the 95% C.I. for the mean difference was 3.3 to 8.5). The mean elimination half-life of quinine when coadministered with rifampicin (5.5 +/- 3.0 h) was significantly shorter than when quinine was given alone (11.1 +/- 3.0 h; the 95% C.I. for the mean difference was -8.6 to -2.6). In contrast to rifampicin, pretreatment for 1 week with 300 mg oral isoniazid had no significant effects on the pharmacokinetics of quinine.(ABSTRACT TRUNCATED AT 250 WORDS)
Wanwimolruk
S
S
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Kang
W
W
Coville
P F
PF
Viriyayudhakorn
S
S
Thitiarchakul
S
S
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004357:Drug Synergism; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011803:Quinine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*; D013785:Thailand
D000962:Antimalarials; D000995:Antitubercular Agents; D011803:Quinine; D007538:Isoniazid; D012293:Rifampin