RESUMO
One hundred and five healthy nonimmunes in Colombia took part in a randomize, double-blind comparison of 250 mg of Lariam (L) (active ingredient: mefloquine) on alternate weeks or one tablet of Fansidar (F) (active ingredients: sulfadoxine and pyrimethamine) weekly for malaria prophylaxis during at least six months. Volunteers also gave blood for determination of drug concentrations after six months and/or 24-27 months of prophylaxis. Twenty-five volunteers withdrew involuntarily when they lost their jobs in the company. Two who took L withdrew due to moderate diarrhea and mild nausea or headache, weakness, drowsiness and anxiety. One volunteer stopped taking F due to severe unilateral hypostatic eczema and slight S-T depressions on the ECG. The rest completed at least six (range 6-36) months of prophylaxis. The mean half-life for L was 26 days. The AUCs in the time interval 0-14 days for L varied between 19.3-31.5 mumol x days/l. For the main metabolite, the corresponding range was 28.8-81.3 mumol x days/l. The range of trough concentrations at day 0 and 14 were 0.95-2.01 mumol/l for L and 1.69-5.62 mumol/l for the metabolite. No differences in tolerability and efficacy were noted between L and F. Our kinetic results do not indicate that enzymatic induction or inhibition would be important during long-term prophylaxis with mefloquine. This favors a continued use of the drug for very long periods of time (= years).
Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/prevenção & controle , Mefloquina/uso terapêutico , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Adulto , Antimaláricos/efeitos adversos , Antimaláricos/farmacocinética , Método Duplo-Cego , Combinação de Medicamentos , Meia-Vida , Humanos , Modelos Lineares , Masculino , Mefloquina/efeitos adversos , Mefloquina/farmacocinética , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Pirimetamina/efeitos adversos , Pirimetamina/farmacocinética , Sulfadoxina/efeitos adversos , Sulfadoxina/farmacocinéticaRESUMO
The plasma concentrations of sulfadoxine, pyrimethamine, mefloquine and its major metabolite were determined in 18 healthy male volunteers who had regularly taken either 500 mg of sulfadoxine and 25 mg of pyrimethamine (Fansidar) weekly or 250 mg mefloquine regularly every 14 d during 6 months for malaria prophylaxis. The mean trough concentrations of sulfadoxine, pyrimethamine and mefloquine were 194, 0.28 and 1.48 mumol/litre and the mean half lives were 7.7, 4.2 and 25 d respectively. The variation in area under the curve for the 3 drugs was only 2-3 fold. The findings do not indicate that drug accumulation or induction of metabolism occurred during long-term usage.
