Halofantrine pharmacokinetics in Kenyan children with non‐severe and severe malaria.

Abstract

1. Kenyan children with uncomplicated malaria given oral halofantrine (HF; non‐micronised suspension; 8 mg base kg‐1 body weight 6 hourly for three doses) showed wide variation in the disposition of HF and desbutylhalofantrine (HFm). 2. Eight Kenyan children with severe (prostrate) falciparum malaria who were receiving intravenous quinine, were given the same HF regimen by nasogastric tube. One patient had undetectable HF and two had undetectable HFm at all times after drug administration. 3. The mean AUC(0,24 h) of HF in prostrate children was half (7.54 compared with 13.10 micrograms ml‐1 h) (P = 0.06), and that for HFm one‐third (0.84 compared with 2.51 micrograms ml‐1 h) (P < 0.05) of the value in children with uncomplicated malaria. 4. Oral HF may be appropriate for some cases of uncomplicated falciparum malaria in Africa, but in patients with severe malaria, the bioavailability of HF and HFm may be inadequate.

Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria

“…Slow absorption is likely to be a function of the high lipophilicity of piperaquine (log 10 P = 6.157) [35]. Similar absorption profiles are seen with drugs such as halofantrine and tafenoquine which have a low bioavailability when given in the fasting state and improved bioavailability when administered with food [36, 37]. Further work is necessary to define the absorption profile for piperaquine in its various formulations.…”

Stereoselective halofantrine disposition and effect:concentration‐related QTc prolongation

“…The half‐life of accumulation was highly variable but not different between (+)‐ and (−)‐halofantrine. Their values are consistent with previously published data for elimination half‐life [4–8], which could not be usefully evaluated in this study due to variability in plasma concentration data during the washout phase. The extremely high oral clearance of halofantrine probably reflects its low bioavailability following oral administration in the fasted state [5, 9, 10].…”

“…Halofantrine hydrochloride is useful for the treatment of uncomplicated malaria and is effective when used against both chloroquine‐sensitive and chloroquine‐resistant Plasmodium falciparum infections [1–3]. Halofantrine pharmacokinetics have been described in healthy volunteers [4–6] and patients with malaria [6–8]. Following oral administration, the extent of halofantrine absorption is thought to be quite limited and highly variable.…”