Pharmacokinetics of the four combination regimens of dihydroartemisinin/mefloquine in acute uncomplicated falciparum malaria.

The pharmacokinetics of oral dihydroartemisinin and mefloquine were investigated in 40 patients (aged 16-30 y, weighing 45-60 kg) with acute uncomplicated falciparum malaria following the four combination regimens of dihydroartemisinin/ mefloquine [regimen-I: 300 mg dihydroartemisinin (h-0) plus 750 mg mefloquine (h-0); regimen-II: 300 mg dihydroartemisinin (h-0) plus 750 mg mefloquine (h-24); regimen-III: 300 mg dihydroartemisinin (h-0) plus 750 and 500 mg mefloquine (h-24 and 30); regimen-IV: 300 mg dihydroartemisinin (h-0) plus 750 and 500 mg mefloquine (h-0, 24)]. The four combination regimens were well tolerated. Patients in all treatment groups had a rapid initial response. However, 9 patients (4, 4, and 1 cases in regimens-I, II, and IV) had reappearance of parasitemia during the follow-up period. Significant changes in the pharmacokinetic parameters of both mefloquine and dihydroartemisinin were observed in patients with malaria compared with healthy subjects reported in a paralleled study. For mefloquine, Cmax (mg per dose), AUC0-day1 (mg per dose), and AUC0-day7 (mg per dose) were significantly higher in patients. Furthermore, tmax, was prolonged while V/F contracted and tl/2,z, MRT shortened in patients with malaria. For dihydroartemisinin, Cmax AUC, tmax and Vz/F were changed in the same direction as mefloquine, whereas t1/2z and MRT were prolonged. CL/F was also significantly reduced in patients with malaria. Absorption/disposition kinetics of oral dihydroartemisinin were similar among the various regimens. On the other hand, AUC0-day1 (mg per dose) of mefloquine after regimen-III was significantly higher than the other three regimens. Combination regimens with two divided doses of mefloquine (regimens-III and IV) resulted in a significantly delayed tmax (especially regimens-IV) compared with those with single dose regimens (regimens-I and II).

Polygamy: the possibly significant behavior of Aedes aegypti and Aedes albopictus in relation to the efficient transmission of dengue virus.

The polygamous behavior of male Aedes aegypti (L.) and Ae. albopictus (Skuse) was investigated by co-habiting a newly-emerged male and females in a 30 cm3 cage (1 male: 20 females) for up to 5 consecutive days. As determined by insemination rates, the results indicated that one Ae. aegypti and Ae. albopictus male could successfully mate with 1.10 (0-4), 4.10 (1-8), 5.40 (4-8), 5.10 (2-8), 5.15 (3-9) and 0.20 (0-3), 1.70 (0-3), 2.35 (1-4), 2.30 (0-4), 2.35 (1-4) Ae. aegypti and Ae. albopictus females, respectively on day 1,2,3,4 and 5 consecutively. The possibly significant role of their polygamy in relation to dengue virus transmission is discussed.

Comparative morphometry, morphology of egg and adult surface topography under light and scanning electron microscopies, and metaphase karyotype among three size-races of Fasciola gigantica in Thailand.

Comparative morphometry of eggs and adults under light microscope, and morphology of adults under scanning electron microscope (SEM) were undertaken in the three size-races (< 25 mm, 25-35 mm, > 35 mm) of Fasciola gigantica (Thailand strain). Morphometric examination revealed intraspecific variation with respects to the dimensions of eggs and adults, whereas surface topography of the three size-race adults under SEM was morphologically similar. The observations on mitotic metaphase chromosomes of spermatogonial cells from testes of the three size-races revealed 2n=20 (diploid type), and no karyotypic difference was observed among them. The meiotic metaphase chromosome was 10 bivalents in primary spermatocyte in diplotene to diakinesis, and many mature spermatozoa were seen in the testicular preparations.

Investigations of incidence of pretreatment, drug sensitivity in vitro, and plasma levels of pyrimethamine in patients with multidrug resistant falciparum malaria following the three combination regimens of artemether/pyrimethamine.

The study was carried out to investigate the status of in vitro susceptibility of Plasmodium falciparum to pyrimethamine (PYR) in multidrug resistant area of the Thai-Myanmar border, the incidence of unregulated use of the combination of PYR with sulfadoxine (Fansidar) in this area and the relevance of pharmacodynamic and pharmacokinetic factors in determining the treatment outcome from the three combination regimens of ART/PYR (1-, 2- and 3-day regimens), in patients with acute uncomplicated falciparum malaria. The majority of patients had baseline PYR concentrations in the range of 1-100 (50.6%) or 100-500 (34.8%) ng/ml, while concentrations of more than 500 ng/ml were found in only 1.1%. All of the isolates exhibited high grade resistance to PYR with the minimum inhibition concentration (MIC) of as high as 10(-5) M. No association was observed between treatment outcome and the presence of baseline plasma PYR concentrations. In addition, lack of association between plasma concentrations during the acute phase (day-1 and -2) and treatment outcome was found.