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• W2092508738 abstract "The effect of the antimalarial drugs chloroquine (CQ) and primaquine (PQ) on rat liver microsomal drug metabolism has been studied in vitro and in vivo. After acute administration, PQ increased pentobarbitone sleeping time in a dose-related manner [control, 94.0 ± 9.4 min; 10mg/kg, 137.0 ± 2.4 min; 20mg/kg, 197.0 ± 7.5 min; 50 mg/kg, 269.0 ± 2.9 min (means ± S.E.M.)], prolonged zoxazolamine paralysis time (control, 140.0 ± 10.0 min; 50 mg/kg, 341.5 ± 25.6 min) and decreased antipyrine blood clearance from 2.17 ± 0.19 to 0.86 ± 0.12 ml/min. CQ showed no effect on pentobarbitone sleeping time or zoxazolamine paralysis time, but decreased antipyrine clearance from 2.17 ± 0.19 to 1.11 ± 0.18 ml/min. Both drugs inhibited aminopyrine N-demethylase activity, although the concentration required to produce 50% inhibition was much greater for CQ (10 mM) than for PQ (approximately 0.1 mM). Lineweaver-Burk plots showed that CQ inhibited competitively whereas PQ inhibition was apparently non-competitive. Ethoxyresorufin O-deethylase activity decreased by about 40 and 50% in the presence of CQ and PQ respectively (250 nM, equimolar with substrate). There was no evidence of induction following chronic administration of CQ and PQ (50 mg/kg/day for 4 days). There was an apparent decrease in cytochrome P-450 content and aminopyrine N-demethylase activity was decreased. These results demonstrate that PQ and CQ inhibit hepatic drug metabolism both in vitro and in vivo and that PQ appears to be the more potent inhibitor." @default.
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• W2092508738 date "1983-01-01" @default.
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• W2092508738 title "Inhibition of drug metabolism by the antimalarial drugs chloroquine and primaquine in the rat" @default.
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• W2092508738 doi "https://doi.org/10.1016/0006-2952(83)90553-1" @default.
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