Inhibition of ethinyloestradiol and tolbutamide metabolism by quinoline derivatives in vitro

Chemico-biological Interactions
J H Rivière, D J Back

Abstract

The effects of the quinoline derivatives amodiaquine (AQ), chloroquine (CQ), mefloquine (MQ), primaquine (PQ), quinine (Q) and quinidine (QD) on in vitro hepatic metabolism has been studied using as substrates ethinyloestradiol (EE2) and tolbutamide (TOL). The 2-hydroxylation of EE2 and the hydroxylation of TOL were determined in the presence of variable concentrations of each compound. MQ, PQ, AQ and Q significantly inhibited EE2 metabolism at each of the concentrations studied (0.1, 0.2 and 0.5 mM) as shown by an increase in the percentage of unmetabolised EE2. QD significantly inhibited metabolism at 0.2 and 0.5 mM but CQ was without effect. In terms of recovery of 2-OHEE2, PQ was the most potent inhibitor. At an inhibitor concentration of 0.5 mM the order of potency was PQ greater than or equal to MQ greater than or equal to Q greater than or equal to QD greater than or equal to AQ greater than or equal to CQ. TOL hydroxylase activity in control microsomes was 1.52 +/- 0.33 nmol. min-1 X mg protein-1. The order of potency of the inhibitors (0.5 mM) was PQ greater than or equal to MQ greater than or equal to Q greater than or equal to QD greater than or equal to AQ greater than or equal to CQ. These data provide further evid...Continue Reading

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Citations

Jan 1, 1987·European Journal of Clinical Pharmacology·D J Back, J F Tjia
Jan 1, 1988·European Journal of Clinical Pharmacology·J KarbwangA M Breckenridge
Aug 4, 1992·Biochemical Pharmacology·K N BangchangD J Back
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Mar 1, 1994·Transactions of the Royal Society of Tropical Medicine and Hygiene·K N BangchangJ Karbwang
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Mar 23, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G LefèvreM S Thomsen
Jan 1, 1994·Fundamental & Clinical Pharmacology·J Karbwang, K Na-Bangchang
Apr 1, 1990·The Journal of Pharmacy and Pharmacology·D L LancasterM S Lennard
May 8, 1992·Biochemical Pharmacology·K N BangchangD J Back
Jun 1, 2009·Acta Neuropsychiatrica·Snježana Miškov
Jan 31, 2021·Applied Microbiology and Biotechnology·Amin GasmiGeir Bjørklund

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