Effect of Erythromycin, Rifampicin and Isoniazid on the Pharmacokinetics of Quinine in Rats

Abstract

The effects of rifampicin and isoniazid on the pharmacokinetics of quinine were studied in rats. Rats were divided into groups and pretreated with rifampicin (30 mg kg−1, p.o.), isoniazid (25 mg kg−1, p.o.) and a combination of rifampicin and isoniazid, once a day for 14 days before receiving an intravenous bolus dose of quinine (25 mg kg−1). Blood samples were collected at different times, up to 6h after quinine administration. Plasma quinine concentrations were assayed by HPLC. There were no significant differences in mean plasma quinine concentration-time profiles between pretreated and control (t1/2 = 0.94 ± 0.15h; CL = 1.82 ± 0.36 Lh−1 kg−1; Vd=2.46 ± 0.56 L kg−1) groups. The effect of erythromycin on the pharmacokinetics of quinine was also studied. Rats were pretreated with 80 mg kg−1 erythromycin 7 days before administration of quinine. There was no significant difference in the pharmacokinetics of quinine between pretreated and control (t1/2 = 1.24 ± 0.46h; CL = 1.84 ± 0.42Lh−1 kg−1;Vd = 3.32 ± 1.46 L kg−1) groups. The results suggest that erythromycin, rifampicin and isoniazid have no significant effect on the pharmacokinetics of a single intravenous dose of quinine in rats. However, in man there is a marked interaction between quinine and rifampicin. This emphasizes the species differences between P450 enzymes involved in drug metabolism and extrapolation of animal studies to human must be treated with caution.