Publication: Pharmacokinetics, efficacy and toxicity of parenteral halofantrine in uncomplicated malaria
Issued Date
1993-01-01
Resource Type
ISSN
13652125
03065251
03065251
Other identifier(s)
2-s2.0-0027137381
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
British Journal of Clinical Pharmacology. Vol.36, No.6 (1993), 585-591
Suggested Citation
S. KRISHNA, F. Ter KUILE, W. SUPANARANOND, S. PUKRITTAYAKAMEE, P. TEJA‐ISAVADHARM, D. KYLE, N. J. WHITE Pharmacokinetics, efficacy and toxicity of parenteral halofantrine in uncomplicated malaria. British Journal of Clinical Pharmacology. Vol.36, No.6 (1993), 585-591. doi:10.1111/j.1365-2125.1993.tb00419.x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/22802
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Pharmacokinetics, efficacy and toxicity of parenteral halofantrine in uncomplicated malaria
Abstract
The pharmacokinetics, efficacy and toxicity of a new parenteral formulation of halofantrine hydrochloride were evaluated in 12 adults with acute uncomplicated falciparum malaria and nine adults who attended in convalescence. Intravenous halofantrine (1 mg kg−1infused in 1 h) was given every 8 h for a total of three doses in the acute study. Halofantrine cleared parasitaemia rapidly in all but one patient, with a mean (s.d.) parasite clearance time of 71 (29) h. Convalescent patients received a single infusion (1 mg kg−1in 1 h). An open two‐compartment model with the following parameters described the pharmacokinetics of halofantrine in acute malaria (mean (s.d)): V1= 0.36 (0.18) 1 kg−1; CL = 0.355 (0.18) 1 h−1kg−1; t1/2;α= 0.19 (0.12) h; t1/2;β= 14.4 (7.5) h. Intravenous halofantrine in acute malaria produced significant prolongations of the QT and QTcintervals (mean (s.d.)) of 20 (15%) and 8.2 (5.6)%, respectively (P < 0.001) after the third dose, but no clinically significant cardiotoxcity. Eight patients experienced mild to moderate thrombophlebitis at the halofantrine infusion site which had resolved in six by the time of follow‐up. In the single treatment failure who received oral quinine, there was a large rise in plasma halofantrine concentration but this did not result in detectable toxicity. These data provide the basis for the design of improved dosing regimens for the use of parenteral halofantrine in malaria. 1993 The British Pharmacological Society