Efficacy of Multiple-Dose Halofantrine in Treatment of Chloroquine-Resistant Falciparum Malaria in Children in Kenya

Watkins, William A.; Lury, J.D; Kariuki, D.M.; Koech, Davy K.; Oloo, James Aggrey; Mosoba, M; Mjomba, M; Gilles, H. M.

doi:10.1016/s0140-6736(88)92538-x

Cited by 47 publications

(16 citation statements)

References 7 publications

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“…The most effective dose has been 500 mg every 6 h for three doses for 8 mg kg-' 6 hourly for three doses in children (Boudreau et al, 1988;Cosgriffetal., 1982;Coulaud etal., 1986;Rinehart etal., 1976;Watkins et al, 1988;Wirima et al, 1988). In the present study, although it cured 83% (10/12) of the patients, two showed a high degree of resistance (i.e.…”

Section: Discussioncontrasting

confidence: 60%

Pharmacokinetics of halofantrine in Thai patients with acute uncomplicated falciparum malaria.

Karbwang

Milton

Bangchang

et al. 1991

Brit J Clinical Pharma

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Twelve patients with acute uncomplicated falciparum malaria were admitted to the Hospital for Tropical Diseases for 42 days. The patients were treated with halofantrine 500 mg 6 hourly for three doses and halofantrine and its desbutyl metabolite were analysed in plasma by h.p.l.c. Cmax values of halofantrine and desbutylhalofantrine (n = 12) were 1192 ± 410 (mean ± s. d.) and 397 ± 160 ng ml-' with tmax values of 16 ± 2 and 55 ± 26 h, respectively. AUC was 60.6 ± 23.9 and 48.5 ± 22.2 mg 1-1 h, respectively, for halofantrine and its metabolite. Halofantrine cured 83% of the patients but in two patients a reduction only in asexual parasitaemia was seen and no overall parasite clearance occurred. One of these, however had relatively low plasma concentrations of both halofantrine and its desbutyl metabolite and it appeared to be a case of inadequate treatment rather than true resistance. We suggest that the large intersubject variability in plasma drug concentrations may relate in part to its poor and inconsistent bioavailability and this rather than true resistance might be responsible for some of the treatment failures.

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Section: Discussioncontrasting

confidence: 60%

Pharmacokinetics of halofantrine in Thai patients with acute uncomplicated falciparum malaria.

Karbwang

Milton

Bangchang

et al. 1991

Brit J Clinical Pharma

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“…16 1 8 It has proved to be effective in the treatment of drug-resistant strains of P. falciparum in semi-immune patients in various geographic localities. [8][9][10][11][12][13] In this study, we show that halofantrine is 100% effective in the treatment of malaria in nonimmune patients if a regimen including a second treatment on day 7 is applied. A similar experience was reported by Bernard and others, 14 who successfully treated 59 patients from tropical Africa with a two-day course of halofantrine on days 1 and 8.…”

Section: Discussionmentioning

confidence: 99%

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

Weinke¹,

Löscher²,

Fleischer³

et al. 1992

The American Journal of Tropical Medicine and Hygiene

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“…Previous studies have shown that halofantrine is an effective drug for the treatment of acute falciparum malaria in areas of chloroquine resistance in Africa (17,19,20).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of micronized halofantrine in semi-immune patients with acute uncomplicated falciparum malaria in Cameroon

Fadat

Louis

et al. 1993

Antimicrob Agents Chemother

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Fifty subjects with acute uncomplicated falciparum malaria were treated orally with a new micronized formulation of halofantrine. The dose given corresponded to one-half the normal dose for the standard formulation. Parasitemia cleared in all subjects within 78 h. There was recrudescence of falciparum malaria in seven subjects after day 14. The mean standard deviation clearance times of parasitemia and fever were 49.0 14.2 and 24.3 13.2 h, respectively. Other clinical symptoms related to malaria cleared within the first 3 days. Pruritus occurred in two subjects, back pain occurred in one subject, and diarrhea occurred in one subject; all of these symptoms were mild. Hematological and biochemical indices were not adversely affected by treatment except in five subjects in whom minor and transitory increases in aspartate aminotransferase and alanine aminotransferase were observed. Micronized halofantrine appears to be a safe, well-tolerated, and effective treatment for acute falciparum malaria in semiimmune patients.The spread of chloroquine-resistant Plasmodium falciparum to most countries in Africa has prompted the development of alternative drugs for the treatment of malaria. Halofantrine has been used since 1988 in France and some West and Central African countries and was demonstrated to be effective in treating resistant falciparum malaria (5, 10, 17). However, a major drawback of halofantrine is its poor and variable absorption and bioavailability between subjects; these have been responsible for a number of treatment failures (3,11,12,15,18 greater, respectively. These doses correspond to one-half the normal dose for the standard formulation of halofantrine (25 mg/kg of body weight). The drug was administered to patients without a specific food regimen. Patients were followed at home, and the intake of the doses was supervised. Investigations including clinical examination, temperature, symptom recording, and blood smears were performed twice daily for the first 4 days and on days 7, 14, 21, and 28 posttreatment. Parasite counts on blood smears were determined twice daily until two successive thick blood smears were negative.Routine blood examinations (hematocrit, hemoglobin, erythrocyte count, total leukocyte count, and platelet count) were performed before treatment and on days 3, 7, 14, 21, and 28 posttreatment.Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase, bilirubin, and creatinine were measured before treatment and on days 3, 7, and 28 posttreatment.In vitro antimalarial drug susceptibilities (chloroquine, quinine, and halofantrine) were assessed before treatment by an isotopic semimicrotest (13). Briefly, a suspension (700 ,ul per well) of parasitized erythrocytes (1.5% hematocrit, 0.2 to 0.5% initial parasitemia) in RPMI 1640 medium supplemented with 10% human serum and buffered with 25 mmol of N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) per liter and 25 mmol of NaHCO3 per liter was distributed in predosed 24-well plates. The plates were incu...

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Efficacy of Multiple-Dose Halofantrine in Treatment of Chloroquine-Resistant Falciparum Malaria in Children in Kenya

Cited by 47 publications

References 7 publications

Pharmacokinetics of halofantrine in Thai patients with acute uncomplicated falciparum malaria.

Pharmacokinetics of halofantrine in Thai patients with acute uncomplicated falciparum malaria.

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

Efficacy of micronized halofantrine in semi-immune patients with acute uncomplicated falciparum malaria in Cameroon

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