A further interaction study of quinine with clinically important drugs by human liver microsomes: determinations of inhibition constant (Ki) and type of inhibition

  • X-J. Zhao
  • T. Ishizaki

DOI: 10.1007/BF03190031

Cite this article as:
Zhao, XJ. & Ishizaki, T. Eur. J. Drug Metab. Pharmacokinet. (1999) 24: 272. doi:10.1007/BF03190031


Our previous study showed that several drugs inhibited quinine 3-hydroxylation, a cytochrome P450 (CYP) 3A4-mediated reaction,in vitro. In this extended study, 13 drugs were selected and tested by human liver microsomes in order to further determine their respective inhibition constant (Ki) and type of inhibition. According to the apparent Ki values, the inhibitory rank order of these tested drugs was as follows: ketoconazole > doxycycline > omeprazole > tetracycline > troleandomycin (with pre-incubation) > primaquine > troleandomycin (without pre-incubation) > nifedipine > erythromycin > verapamil > oleandomycin > diltiazem > cimetidine > hydralazine. Among these drugs, doxycycline, tetracycline, ketoconazole, nifedipine and hydralazine were judged as mixed inhibitors; whereas, the remaining other drugs tested were judged as competitive inhibitors. When the plasma/serum concentrations possibly attained after their usual therapeutic doses were taken into account, tetracycline, doxycycline, omeprazole, ketoconazole, nifedipine, troleandomycin and erythromycin are likely to be inhibitors of quinine metabolism in patients when these drugs are co-administrated with quinine.


Quinine 3-hydroxylation drug interactions human liver microsomes CYP3A 

Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • X-J. Zhao
    • 1
  • T. Ishizaki
    • 1
  1. 1.Department of Clinical Pharmacology, Research InstituteInternational Medical Center of JapanTokyoJapan
  2. 2.Indiana University School of Medicine, Department of Medicine, Division of Clinical PharmacologyWishard Memorial HospitalIndianapolisUSA
  3. 3.Department of Pharmacology and Therapeutics, Graduate School of Clinical PharmacyKumamoto UniversityKumamotoJapan

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