Effects of tetracycline on the pharmacokinetics of halofantrine in healthy volunteers.

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Bassi PU, Onyeji CO, Ukponmwan OE

Effects of tetracycline on the pharmacokinetics of halofantrine in healthy volunteers.

Br J Clin Pharmacol. 2004 Jul;58(1):52-5. doi: 10.1111/j.1365-2125.2004.02087.x.

PubMed ID

15206992 [ View in PubMed

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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 microg ml(-1) (95% CI on the difference 0.30, 0.95); AUC 32.0 +/- 13.6 vs 63.7 +/- 20.1 microg 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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Tetracycline	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details