A total of 141 cases of strictly defined cerebral malaria were studied in a controlled trial of three regimens: (1) intramuscular artemether plus oral mefloquine, (2) intravenous artesunate plus oral mefloquine, and (3) intravenous quinine (with or without an initial loading dose) plus oral tetracycline. The overall mortalities in each group were 14%, 8.3% and 34.3% respectively. The average parasite clearance time was 27.30 +/- 19.62 hours in regimen 1, 41.84 +/- 17.55 hours in regimen 2, and 47.30 +/- 21.95 hours in regimen 3.
A randomized comparative trial of the pharmacokinetics and pharmacodynamics of oral doses of mefloquine and of mefloquine in combination with artesunate was carried out on 20 Thai male patients with acute, uncomplicated falciparum malaria. The patients were randomized to receive either mefloquine alone (8 patients; 1250 mg of mefloquine--initial dose, 750 mg; followed 6 hours later by 500 mg), or in combination with oral artesunate (12 patients--initial dose, 200 mg of artesunate; followed by 750 mg and 500 mg of mefloquine 6 hours and 12 hours later, respectively).
The in vitro effect of the following antimicrobial agents on Toxoplasma gondii tachyzoites were studied: artemisinin ether (arteether), cycloguanil hydrochloride (cycloguanil), mefloquine, primaquine phosphate, and quinine sulfate, as well as the calcium channel blocker verapamil and the calmodulin inhibitor trifluoperazine hydrochloride. Arteether at > or = 0.5 micrograms/ml and cycloguanil at > or = 1.0 micrograms/ml inhibited T. gondii in vitro. Cycloguanil (2.5 micrograms/ml) combined with a noninhibitory concentration of sulfadiazine (25 micrograms/ml) inhibited T.
1. The aim of this study was to assess the pharmacokinetics, clinical efficacy and safety of artemisinin alone and in combination with mefloquine. 2. Thirty-eight adults with symptomatic Plasmodium falciparum malaria were randomly assigned to receive either artemisinin (500 mg single dose followed by another 500 mg on day 1 and then 250 mg twice daily for 4 days) or artemisinin (500 mg single dose followed by 750 mg on day 1 and then 250 mg three times daily for one more day) in co-administration with mefloquine (250 mg three times daily for the first day).
The activity of artemisinin in combination with mefloquine was tested in vitro against a chloroquine-sensitive (F32) strain of Plasmodium falciparum. A method of repetitive dosing and extending the culture observation period to 28-30 days was used to mimic the in vivo pharmacokinetic situation. Plasmodium falciparum was exposed to artemisinin from 10(-8) to 10(-5) M, mefloquine from 3 x 10(-9) to 10(-5) M and their combinations. The exposure time for artemisinin was 3 hours twice daily and for mefloquine 24 hours. The drug-dosing duration was 3 days.
AIMS: Multi-drug resistant Plasmodium falciparum malaria is a rapidly increasing problem in the world, particularly Thailand. Practical antimalarial regimens which are highly effective against multi-drug resistant parasites with short-term course of administration are needed. In this study, we assessed the patient compliance of a short course regimen using artemether-mefloquine.
To characterize post-treatment clearance of young forms of Plasmodium falciparum from the blood, three differential equation models, a linear decline, a linear then logarithmic decline, and the Michaelis-Menten (MM) kinetic equation, were fitted to log-transformed serial parasite counts from 30 semi-immune patients with synchronous parasitaemias allocated one of six antimalarial drug regimens. The first two equations were solved analytically. The MM equation was solved numerically using a fifth-order Runge-Kutta method.
An open, randomized comparison of artemether-benflumetol (CGP 56 697; Novartis) with artesunate-mefloquine was conducted in 617 patients with acute uncomplicated multidrug-resistant falciparum malaria on the western border of Thailand. Both treatments rapidly and reliably cleared fever and parasitemia, and there was no significant difference in the initial therapeutic response parameters. Parasite genotyping was used to distinguish recrudescences from new infections.
The American Journal of Tropical Medicine and Hygiene
A randomized pilot study to compare the safety and efficacy of artesunate suppositories (15 mg/kg/day for three days) versus oral artesunate (6 mg/kg/day for three days), both in combination with mefloquine (25 mg/kg), was conducted in 52 Thai children with uncomplicated multidrug-resistant falciparum malaria. Forty-five patients (87%) had a full 28-day follow-up in the hospital to assess efficacy and exclude reinfection. Mean [range] times to fever clearance of the two groups were similar (42 hr [15-104] versus 42 hr [6-119]).
The American Journal of Tropical Medicine and Hygiene
The in vitro activity of artemether against 56 African isolates of Plasmodium falciparum from Senegal was evaluated using an isotope-based drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 15.2 nM (mean IC50 = 3.43 nM) and the 95% confidence interval (CI) was 2.50-4.36 nM. Artemether was equally effective on chloroquine-sensitive and chloroquine-resistant isolates (mean IC50 = 346 nM, 95% CI = 2.08-4.84 nM versus mean IC50 = 2.80 nM, 95% CI = 2.00-3.60 nM).