Oral bioavailability of sulphamethoxydiazine, sulphathiazole and sulphamoxole in dwarf goats.

To get a better insight into the oral bioavailability of sulphonamides in ruminants, sulphamethoxydiazine (pKa 7.0), sulphathiazole (pKa 7.2), and sulphamoxole (pKa 7.4) were administered to dwarf goats (n = 5). The drugs were given at 2-week intervals by the intravenous or intraruminal route at a dose of 100 mg per kg body weight. After IV injection, the mean half-life (t1/2 beta in h +/- SEM) was 0.80 +/- 0.10 h, 2.35 +/- 0.38 h, and 3.36 +/- 1.25 h, for sulphathiazole, sulphamoxole, and sulphamethoxydiazine, respectively and the mean distribution volume (Vd beta) was 0.23 +/- 0.05 l/kg, 0.23 +/- 0.04 l/kg, and 0.33 +/- 0.02 l/kg. After intraruminal administration, the mean bioavailability varied from 86.0 +/- 11.8% for sulphamethoxydiazine to 46.6 +/- 4.3% for sulphamoxole, and 52.6 +/- 7.2% for sulphathiazole. The elimination half-life was significantly prolonged, probably due to a low rate of drug absorption from the gastrointestinal tract. In contrast to chloramphenicol, the sulphonamides studied were stable when incubated in rumen fluid at 39 degrees C.

Pancytopenia in a patient given pyrimethamine and sulphamethoxidiazine during pregnancy.

This is a report of a pregnant woman who became pancytopenic in the second trimester following pyrimethamine administration. The patient recovered on steroid, antibiotics, transfusion, folic acid and folinic acid therapy, and the pregnancy was uneventful afterwards. The patient was delivered of a healthy term-infant.

Treatment of chloroquine-resistant malaria during pregnancy.

A pregnant 36-year-old Vietnamese refugee with chloroquine-resistant Plasmodium falciparum infection was treated with pyrimethamine and a sulfonamide. This treatment produced rapid clearance of the patient's parasitemia and was associated with a resumption of normal fetal and uterine growth. Because the other drugs effective against chloroquine-resistant P falciparum may produce uterine stimulation (quinine sulfate) or damage the fetal skeleton (tetracyclines), the pyrimethamine-sulfonamide combination (with folinic acid supplementation) may be the best available choice for the treatment and prophylaxis of chloroquine-resistant P falciparum infection in pregnancy, despite its theoretical risk of teratogenicity.

[A comparison of Ultrax, Diazil, Bactrim and Spiramycin in experimental toxoplasmosis in mice (author's transl)]. / Vergleichende Untersuchung der Wirksamkeit von Ultrax, Diazil, Baktrim und Spiramycin auf die experimentelle Toxoplasmose der Maus.

White mice infected intraperitoneally with the RH-strain of Toxoplasma gondii (inoculum size 50,000 to 100,000 free protozoans per mouse) received treatment between the second and eighth day after infection with sulphamethazine-pyrimethamine, sulphamethoxy-diazine-pyrimethamine, trimethoprim-sulphamethoxazole or spiramycin subcutaneously. All untreated controls and all mice of the trimethoprim-sulphamethoxazole and spiramycin-treated groups died during the acute stage (except two mice in the latter group on the 15th day). The mean survival times were 6.5, 7.5 and 7.6 days, respectively. The best results were obtained in the sulphamethazine-pyrimethamine-treated mice; 18 out of 27 survived the 30-day observation period (5 cured), in contrast to only 9 out of 40 sulphamethoxydiazine-pyrimethamine-treated mice. Considering the high pathogenicity of the RH-strain, the differences in immunological defence mechanisms in mice (absence of antibody-activating "accessory factor") and the late commencement of treatment of the infected mice, one can state that the combination of sulphamethoxydiazine-pyrimethamine should also be capable of overcoming acute human toxoplasmosis in pregnancy. Spiramycin, by contrast, should be given only in cases where sulphonamide intolerance exists and must then be given in high doses until delivery. The combination of sulphamethoxazole-trimethoprim cannot be recommended.