Effects of tetracycline on the pharmacokinetics of halofantrine in healthy volunteers

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.

Figure 1

Mean (± SD) plasma concentration vs time profiles for halofantrine (A) HF alone (□), HF with TCN (▪); and HFM (B) HFM (without TCN) (□), HFM (TCN presence) (▪); following oral administration of single doses of 500 mg of halofantrine HCl alone, and with tetracycline (TCN, 500 mg 12 hourly for 7 days), to eight subjects