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Marked enhancement by rifampicin and lack of effect of isoniazid on the elimination of quinine in man.
Author(s) -
Wanwimolruk S,
Kang W,
Coville PF,
Viriyayudhakorn S,
Thitiarchakul S
Publication year - 1995
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1995.tb04541.x
Subject(s) - quinine , rifampicin , isoniazid , pharmacology , medicine , malaria , tuberculosis , immunology , pathology
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)