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.
RCT Entities:
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.
Authors: Yetunde T Kolade; Chinedum P Babalola; Ajibola A Olaniyi; Gerhard K E Scriba Journal: Eur J Clin Pharmacol Date: 2007-10-20 Impact factor: 2.953
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Authors: Xin Hui S Chan; Yan Naung Win; Ilsa L Haeusler; Jireh Y Tan; Shanghavie Loganathan; Sompob Saralamba; Shu Kiat S Chan; Elizabeth A Ashley; Karen I Barnes; Rita Baiden; Peter U Bassi; Abdoulaye Djimde; Grant Dorsey; Stephan Duparc; Borimas Hanboonkunupakarn; Feiko O Ter Kuile; Marcus V G Lacerda; Amit Nasa; François H Nosten; Cyprian O Onyeji; Sasithon Pukrittayakamee; André M Siqueira; Joel Tarning; Walter R J Taylor; Giovanni Valentini; Michèle van Vugt; David Wesche; Nicholas P J Day; Christopher L-H Huang; Josep Brugada; Ric N Price; Nicholas J White Journal: PLoS Med Date: 2020-03-05 Impact factor: 11.069