IngentaConnect Effects of tetracycline on the pharmacokinetics of halofantrine i...

Authors: Bassi P.U.¹; Onyeji C.O.; Ukponmwan O.E.²

Source: British Journal of Clinical Pharmacology, Volume 58, Number 1, July 2004 , pp. 52-55(4)

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. Conclusions

Tetracycline co-administration significantly increases the plasma concentrations of halofantrine and its major metabolite.

Keywords: halofantrine; interaction; pharmacokinetics; tetracycline

Document Type: Research article

DOI: 10.1111/j.1365-2125.2004.02087.x

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

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Effects of tetracycline on the pharmacokinetics of halofantrine in healthy volunteers