Acute psychosis after mefloquine. Report of six cases.

A self-limiting psychosis characterized by acute onset of visual and auditory hallucinations and poor sleep developed in six adults between 8 and 24 hours after oral administration of 750-1500 mg of the antimalarial mefloquine. All patients had no personal or family history of psychosis and were neurologically and mentally normal before mefloquine ingestion. These cases illustrate that acute psychotic symptoms may occur in patients treated with mefloquine.

Mefloquine-sulphadoxine-pyrimethamine (Fansimef, Roche) in the prophylaxis of Plasmodium falciparum malaria: a double-blind, comparative, placebo-controlled study.

From July 1987 to June 1988 a randomized, double-blind, comparative placebo-controlled field trial was conducted in a group of villages near Ibadan, Nigeria. The aim of the study was to assess the suppressive tolerability and efficacy of four antimalarials (Fansimef, Lariam, Fansidar, chloroquine) given for 24 weeks. Fansimef and Lariam were given with loading and maintenance doses, Fansidar and chloroquine as one tablet per week for 24 weeks. Of 567 enrolled subjects, 114 (20%) had parasitaemia on entry. Eight episodes of symptomatic falciparum malaria occurred during the trial, seven in the placebo group, and one in the Fansimef group. Compared with placebo, parasitaemia was effectively suppressed by all four drug regimens. Adverse event data were not significantly different between groups: six adverse events per 114 participants in the Fansimef group, six/113 in the mefloquine group, five/111 in the Fansidar group, 17/115 in the chloroquine group and eight/114 in the placebo group. Safety of Fansimef for 24 weeks in endemic areas was comparable for standard antimalarials in this trial and provides support for the use of this drug for the treatment of resistant malaria in indigenous African populations.

Parenteral sulphadoxine-pyrimethamine (Fansidar): an effective and safe but under-used method of anti-malarial treatment.

One hundred and eighteen patients with acute falciparum malaria were randomized into treatment with either intramuscular or oral sulfadoxine-pyrimethamine (Fansidar, Roche) and the results were compared with those from 68 patients treated in parallel with chloroquine. Parasitological cure rate was 97% with oral sulfadoxine-pyrimethamine, 95% with the injection, and only 63% with chloroquine. The time for the disappearance of parasitaemia in sensitive cases was the same with oral and intramuscular sulfadoxine-pyrimethamine and shorter than with chloroquine. Side effects occurred in only 3 of the patients treated with intramuscular sulfadoxine-pyrimethamine compared with 8 of those treated with the tablets and 13 of those treated with chloroquine. The results showed that intramuscular sulfadoxine-pyrimethamine is as effective as, and probably better tolerated than, the oral drug. Increasing failure of response to chloroquine in Nigeria was also demonstrated.

Inhibition of metoprolol metabolism by chloroquine and other antimalarial drugs.

The ability of a series of antimalarial drugs to impair the metabolism of metoprolol in rat and man has been examined. Chloroquine was a potent inhibitor in rat liver microsomes (Ki value for metoprolol alpha-hydroxylation = 0.18 microM and for O-demethylation = 0.36 microM). The other antimalarial drugs also inhibited metoprolol oxidation. Quinine was similar to chloroquine in potency, while quinidine, primaquine and mefloquine were slightly less potent. Chloroquine also inhibited metoprolol oxidation in human liver microsomes, although it was about two orders of magnitude less potent than in the rat and the extent of impairment varied greatly between individual livers. Intraperitoneal administration of chloroquine to anaesthetized rats decreased the clearance of metoprolol (40 mg tartrate salt kg-1 i.p.) to 54, 34, 20 and 26% of the control value at doses of 2.5, 4.0, 25 and 40 mg kg-1, respectively. We conclude that antimalarial treatment might have contributed to a previously reported difference in the metabolic pattern of metoprolol between Caucasians and Nigerians.

Sensitivity of Plasmodium falciparum to mefloquine-sulphadoxine-pyrimethamine (Fansimef) in vivo and to mefloquine alone in vitro in Nigeria.

In Nigeria chloroquine remains the drug of choice for the treatment of falciparum malaria, since chloroquine resistance is not yet a problem. Nevertheless, in view of the rapid spread of multi-resistant Plasmodium falciparum in Africa it is desirable to test alternative drugs for efficacy and safety. To this end, we undertook a comparative controlled trial of the new triple combination, mefloquine-sulphadoxine-pyrimethamine (MSP, Fansimef) with chloroquine in a group of Nigerian children with symptomatic falciparum malaria. Our results showed that Fansimef was an effective blood schizontocide against the Nigerian strain of P. falciparum and was well tolerated. In particular, sinus bradycardia, which was frequently observed with Fanismef in the trials conducted in Zambia, was not seen in any of the Nigerian patients. In vitro sensitivity tests done on 26 P. falciparum isolates showed that all isolates were susceptible to complete inhibition by mefloquine, but the minimum concentration which produced complete inhibition in some isolates was higher than expected for fully sensitive parasites.

beta-Adrenoceptor blocking effects and pharmacokinetics of pindolol. A study in hypertensive Africans.

The beta-adrenoceptor blocking effects of pindolol were compared with those of a placebo in a double-blind trial in twelve hypertensive Africans. Heart rate and arterial blood pressure were measured at rest and immediately after exercise, before and at intervals up to 8 h after oral administration of the drugs. Plasma levels of pindolol were also determined. Pindolol reduced systolic blood pressure and antagonised exercised-induced tachycardia. The mean time to peak level of pindolol was 1.9 h and the mean half-life was 4.2 h. Comparison of plasma levels of pindolol and beta-adrenoceptor blocking activity showed good correlation between them. It is concluded that the pharmacokinetics and beta-blocking effects of pindolol in Africans are not dissimilar from published data for other races.

Pharmacokinetics of pindolol in Africans.

The pharmacokinetics of pindolol were determined in 12 hypertensive African subjects after a single oral dose of the drug. The estimated pharmacokinetic parameters do not differ significantly in Africans from the values which have been obtained in other races.