Pharmacokinetics and clinical experiences of the combination sulfadiazine-trimethoprim in the short-term treatment of acute urinary tract infections.

The pharmacokinetics of sulfadiazine (SD) combined in a small dose (250 mg) with trimethoprim (TMP, 160 mg) and given twice daily were studied in eight healthy subjects. Both drugs were rapidly absorbed from the gastrointestinal tract and their concentrations in serum as well as in urine could be considered high enough for the treatment of acute urinary tract infections (UTI). In none of the subjects did the concentration of SD in urine exceed the experimental limit established for crystallization of the drug. Serum half-lives of SD and TMP were 10.8 and 11.8 hrs, respectively. In microbiological assay synergistic interaction was found in human urine with both the combination of SD + TMP and SM (sulfamethoxazole) + TMP on all the tested strains of E. coli, Str. faecalis, Str. agalactiae, Klebsiella pneumoniae and Proteus mirabilis. A double-blind clinical trial was carried out with patients having acute UTI, using either the combination SD + TMP (250 mg + 160 mg) or the combination SM + TMP (800 mg + 160 mg) twice daily for one week. The results of the treatment were equally successful in both groups. Treatment failed in only 4 out of 85 cases, although in 12 cases the causative micro-organism was resistant in vitro to the combination of SM + TMP.

Effect of vehicle on pilocarpine-induced ocular hypotension.

The effect of 1.4% polyvinyl alcohol and castor oil vehicles on pilocarpine-induced hypotension was studied in 50 patients with open-angle glaucoma. Diurnal tension curves showed that the mean intraocular pressure was lower and the maximum diurnal variation smaller during the treatment with oily drops of 2% and 4% pilocarpine instilled 2-3 times daily than when 2% and 4% pilocarpine in polyvinyl alcohol was instilled 3-4 times daily. The differences were statistically significant. In long-term treatment no marked pilocarpine tolerance developed in cases treated with oily drops of pilocarpine. It is concluded that in the treatment of patients with open-angle glaucoma, the hypotensive effect of pilocarpine in an oily vehicle instilled 2-3 times daily is greater and more even than that of pilocarpine of corresponding strength in polyvinyl alcohol administered 3-4 times daily.

Effect of vehicle on pilocarpine-induced miosis.

To determine the effect of 1.4% polyvinyl alcohol (PVA) and castor oil vehicles on the pilocarpine-induced miosis, we studied the miotic effect of 2% pilocarpine-PVA and oily drops on 4 young and 10 elderly people and the miotic effect of 4% pilocarpine-PVA and oily drops on 13 elderly people. The miosis developed fast within 15 min, and maximum miosis was rached within 1 h. Oily drops of pilocarpine induced stronger maximum miosis than corresponding PVA-drops. The pupil remained contracted to less than 50% of its starting diameter after pilocarpine-PVA drops for 3-4 h and after oily drops for 9 h and returned to its starting diameter after pilocarpine-PVA drops 9-10 h and after oily drops 20-24 h following administration. The difference in the effect between pilocarpine-PVA and oily drops was independent of the subjects' age.

Treatment of hypertension successively with a diuretic, clonidine or a beta-blocking agent and hydralazine.

The present study was carried out in an homogenous group of 49 untreated hypertensive patients, all aged 45 years. Diastolic blood pressure was equal to or greater than 110 mmHg in successive measurements; eleven patients were classified as WHO group II, and the others as WHO group I. An initial placebo period of 3 weeks was followed by cyclothiazide medication with a good response in 6 patients. The remaining patients were given either clonidine or practolol, and by adjustment of the dose a good response was obtained in 31 patients. In these cases the treatment was exchanged after 6 weeks. The antihypertensive effect of relatively small doses of clonidine was equal to that of practolol. Since completion of the study practolol has been withdrawn because of the emergence of long term toxic effects. In 12 cases, hydralazine had to be added to obtain a satisfactory response. Mild side-effects were common, especially at the beginning of clonidine treatment, but they did not necessitate discontinuation of treatment. Further comparative studies of clonidine and beta-blockers should be carried out and more experience with the combination of clonidine and vasodilators in the treatment of hypertension is necessary.