Metabolism of quinine in man: identification of a major metabolite, and effects of smoking and rifampicin pretreatment.
Our previous studies have shown that cigarette smoking and rifampicin pretreatment enhance the elimination of quinine, metabolism assumed, by analogy with quinidine, to be carried out by CYP3A (P450IIIA). This finding is unexpected since it has been shown that smoking induces the CYP1A rather than the CYP3A enzyme family, suggesting that the metabolism of quinine may be catalysed by CYP1A. Therefore, we conducted this study to identify possible quinine metabolites in human urine and to determine which metabolic pathway is induced by cigarette smoking and rifampicin pretreatment. A specific HPLC procedure was employed to identify metabolites of quinine in urine samples collected from healthy volunteers after an oral dose of 600 mg quinine sulphate. The results showed that there were at least seven possible metabolites of quinine detected in human urine. Three of these were identified as 2'-oxoquininone, quinine glucuronide and 3-hydroxyquinine. The 3-hydroxyquinine appeared to be a major metabolite of quinine in urine samples from every subject who took an oral dose of quinine. Although cigarette smoking and rifampicin pretreatment were shown to cause a marked increase in the elimination of quinine there were no significant changes in the formation of 3-hydroxyquinine as measured in the urine samples. This suggests that the effects of smoking and rifampicin are more complicated than we expected and require further investigation.
Wanwimolruk
S
S
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Wong
S M
SM
Zhang
H
H
Coville
P F
PF
Walker
R J
RJ
D000962:Antimalarials / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D011802:Quinidine / Q000031:analogs & derivatives* / Q000032:analysis; D011803:Quinine / Q000378:metabolism*; D012293:Rifampin / Q000494:pharmacology*; D012907:Smoking / Q000378:metabolism*
D000962:Antimalarials; D005965:Glucuronates; C013569:3-hydroxyquinidine; D003577:Cytochrome P-450 Enzyme System; D011803:Quinine; D011802:Quinidine; D012293:Rifampin