The Efficacy of Halofantrine in the Treatment of Acute Malaria in Nonimmune Travelers

Weinke, T.; Löscher, Thomas; Fleischer, K; Kretschmer, H; Pohle, H. D.; Kohler, Benedikt; Schlunk, T.; Clemens, Ralf; Bock, Heinrich

doi:10.4269/ajtmh.1992.47.1.tm0470010001

Cited by 15 publications

(6 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there were no evident pharmacodynamic consequences, in particular no additional prolongation of the QT interval. In another patient we have documented a self-limited episode of encephalitis similar to two other episodes in a much larger study of oral halofantrine [12]. Eosinophilia has not been noted previously after oral treatment with halofantrine, although a delayed eosinophilia does follow treatment with oral quinine [13].…”

Section: Discussionmentioning

confidence: 77%

Pharmacokinetics, efficacy and toxicity of parenteral halofantrine in uncomplicated malaria

Krishna

Kuile

Supanaranond

et al. 1993

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 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. (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. 5 These data provide the basis for the design of improved dosing regimens for the use of parenteral halofantrine in malaria.

show abstract

Section: Discussionmentioning

confidence: 77%

Pharmacokinetics, efficacy and toxicity of parenteral halofantrine in uncomplicated malaria

Krishna

Kuile

Supanaranond

et al. 1993

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4] Therapeutically, it is an important new drug in the context of the continuing spread of resistant strains of malaria. The absolute oral bioavailability of Hf‚ HCl has not previously been fully defined, and plasma profiles of halofantrine (Hf) are erratic and highly variable after oral administration.…”

Section: Introductionmentioning

confidence: 99%

A physicochemical Basis for the Effect of Food on the Absolute Oral Bioavailability of Halofantrine

Humberstone

Porter

Charman

1996

Journal of Pharmaceutical Sciences

122

134

View full text Add to dashboard Cite

Halofantrine hydrochloride (Hf.HCl) is a highly lipophilic phenanthrenemethanol antimalarial. The poor and erratic absorption of Hf after oral administration has been implicated in some treatment failures. Food increases the oral bioavailability of Hf in humans approximately 3-5-fold, although neither the absolute bioavailability nor the basis for the food effect has been fully defined. In this study, the mean (+/-SD, n = 3) absolute oral bioavailability of 250 mg Hf.HCl tablets in beagles was 8.6 +/- 5.3% in the fasted state, which increased approximately 12-fold when administered postprandially. These data indicate that Hf.HCl is efficiently absorbed from the postprandial intestinal environment. The solubility and intrinsic dissolution rate of Hf.HCl were investigated as a function of bile salt concentration (sodium taurocholate, NaTC, 0-30 mM) and micellar composition (4:1 NaTC:lecithin). At premicellar (fasted) concentrations of NaTC (< 5 mM), the solubility and intrinsic dissolution rate were very low (< 15 micrograms/mL; < 0.01 microgram s-1 cm-2). At NaTC concentrations typical of the postprandial state, the solubility and dissolution rate improved dramatically. For example, solubility in 30 mM NaTC increased approximately 1000-fold relative to buffer control, with even greater enhancement (3000-fold) associated with mixed micellar systems. These data suggest that the improved absorption of Hf.HCl in the fed state is most likely due to the increased solubilization and dissolution of the drug in the presence of bile salt mixed micelles.

show abstract

“…Such a high rate has only been reported in trials using a low dose of halofantrine in a single day course regimen [13]. This rate of relapse indicates that the 1-day regimen, which seems effective in semi-immune children, is insufficient in non-immune children and suggests a second course treatment as has been proposed for non-immune adults [12]. However, the benefit risk ratio of a systematic second course treatment must be assessed; the need of a second additional treatment 7 days later has not been clearly established and severe cardiological side-effects after halofantrine therapy have been described [10].…”

Section: Discussionmentioning

confidence: 77%

“…This may be explained by re-infection; relapse could not be distinguished from re-infection acquired before return. Diarrhoea is often observed during malaria, even without intestinal infection [12]. Diarrhoea as a risk factor of a Significant variable treatment failure was described earlier for mefloquine; in this study it appears as the major factor influencing relapses after halofantrine treatment [8].…”

Section: Discussionmentioning

confidence: 82%

“…However, efficacy of halofantrine has been poorly assessed in this population. A 1-day treatment has been shown to be efficacious in semi-immune patients, but unexplained relapses were observed in non-immune patients with imported malaria [4,12]. For this reason, some authors recommended a regimen with a repeated dose after 1 week despite reports of severe cardiological side-effects after treatment and, more recently, severe hepatic disorders [1,2,9].…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Halofantrine efficacy in non-immune children with imported acute Plasmodium falciparum malaria Infection

et al. 2003

View full text Add to dashboard Cite

show abstract

The Efficacy of Halofantrine in the Treatment of Acute Malaria in Nonimmune Travelers

Cited by 15 publications

References 12 publications

Pharmacokinetics, efficacy and toxicity of parenteral halofantrine in uncomplicated malaria

Pharmacokinetics, efficacy and toxicity of parenteral halofantrine in uncomplicated malaria

A physicochemical Basis for the Effect of Food on the Absolute Oral Bioavailability of Halofantrine

Halofantrine efficacy in non-immune children with imported acute Plasmodium falciparum malaria Infection

Contact Info

Product

Resources

About