Effects of tetracycline on the pharmacokinetics of halofantrine in healthy volunteers

doi:10.1111/j.1365-2125.2004.02087.x

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Wiley InterScience

British Journal of Clinical Pharmacology

Volume 58 Issue 1, Pages 52 - 55

Published Online: 22 Apr 2004

The Journal of The British Pharmacological Society

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Effects of tetracycline on the pharmacokinetics of halofantrine in healthy volunteers

Peter U. Bassi ¹ , Cyprian O. Onyeji ² & Otas E. Ukponmwan ³

¹ Department of Clinical Pharmacology, College of Medicine, University of Maiduguri, Maiduguri, Nigeria.,
² Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.,
³ Department of Physiological Sciences, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria

Correspondence to Professor C. O. Onyeji, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria. Tel: + 234 80370 58720 E-mail: conyeji@oauife.edu.ng

KEYWORDS

halofantrine • interaction • pharmacokinetics • tetracycline

ABSTRACT

Aims To investigate the effect of tetracycline co-administration on the pharmacokinetics of halofantrine in healthy subjects.

Methods Eight healthy males were each given 500 mg single oral doses of halofantrine alone, or with tetracycline (500 mg 12 hourly for 7 days), in a crossover fashion. Blood samples collected at predetermined intervals were analyzed for halofantrine and its major metabolite, desbutylhalofantrine (HFM), using a validated HPLC method.

Results Co-administration of tetracycline and halofantrine resulted in a significant increase (P < 0.05) in the maximum plasma concentration (C_max), total area under the concentration-time curve (AUC), and terminal elimination half-life (t_1/2,z), compared with halofantrine alone. (C_max 0.43 ± 0.14 vs 1.06 ± 0.44 µg ml⁻¹ (95% CI on the difference 0.30, 0.95); AUC 32.0 ± 13.6 vs 63.7 ± 20.1 µg ml⁻¹ h (95% CI 14.2, 49.1); t_1/2,z: 90.8 ± 17.9 vs 157.4 ± 57.4 h (95% CI 21.7, 111.5)). Similarly, tetracycline caused a significant increase (P < 0.05) in the AUC and C_max of HFM.