Quinine toxicity when given with doxycycline and mefloquine.

The pharmacokinetic and dynamic interactions among 3 antimalarials, ie quinine, doxycycline and mefloquine was observed in a 26-year-old Thai male patient with falciparum malaria. During the acute episode of the infection, the patient was treated with an intravenous dose of quinine hydrochloride at 600 mg qid, together with an oral dose of doxycycline 100 mg bid. Due to nausea, tinnitus and the persistence of parasitemia in peripheral blood smears, the dose of quinine was reduced 2 days after the first treatment to 300 mg; concurrently oral mefloquine 750 mg was given as 2 divided doses at 24 hours apart. During the course of treatment, the patient developed hearing loss; deafness of the right ear lasted for one week after stopping quinine administration. Higher plasma quinine and lower whole blood mefloquine concentrations than would be expected from the simulation profiles were detected 4 days after the first treatment. However, the concentration of mefloquine was increased upon the cessation of quinine treatment.

Mefloquine level monitoring in patients with multidrug resistant Plasmodium falciparum on the Thai Myanmar border.

A total of 42 patients with uncomplicated falciparum malaria who attended the malaria clinic in Mae Sot, Tak Province were treated with single oral dose of MSP 3 tablets (Fansimef, equivalent to 750 mg of mefloquine) concurrently with primaquine (30 mg). They all contracted the infection from Cambodia. The aim of the study was to monitor the efficacy of MSP 3 tablets for the treatment of this highly multiple drug resistant strains of Plasmodium falciparum in this area. Of the 39 patients included for efficacy assessment, 13 (33.3%) patients had sensitive responses, whereas 15 (38.5%) and 8 (20.5%) had RI and RII types of response, respectively. Melfoquine concentrations on Day-3 after treatment in patients with sensitive and treatment failure groups were comparable; the respective mean (SD) values were 665 (279) and 772 (264) ng/ml.

Pharmacokinetics of prophylactic mefloquine in Thai healthy volunteers.

Malaria constitutes one of the most serious public health problems in Thailand. The disease undermines the health of the people and threatens the economy and security of the country as it is most prevalent in the rural region in forested mountain areas along the border where government officials (border police) have to perform their duties. A safe and effective prophylactic drug for use by these government officials is needed. Nine healthy border police volunteers who were working on the Thai-Cambodia border, aged between 22 to 50 years, and whose weight ranged between 48 and 61 kg, with no history of liver or kidney disease were recruited into the study. 375 mg of mefloquine (as Fansimef tablets) was given as a loading dose, followed by 250 mg every 4 weeks for 4 doses. Whole blood concentrations of mefloquine were measured by high performance liquid chromatography at intervals for 19 weeks. None of the volunteers developed malaria during study period. Seven volunteers had mild adverse effects which required no specific treatment. No changes in liver or renal function or in blood profiles occurred during 19 weeks of observation. Pharmacokinetic analysis revealed a mean maximum concentration of 420 +/- 141 ng/ml a time to peak concentration of 12 +/- 8 hours, terminal half-life was 14.93 +/- 4.43 days, apparent volume of distribution (Vd/f) was 16.5 +/- 5.6 l/kg and total clearance was 0.99 +/- 0.62 ml/min/kg. The mean minimum whole blood mefloquine concentration derived from this study was approximately 100 ng/ml which is considered to be low for treatment.(ABSTRACT TRUNCATED AT 250 WORDS)