Hannu Sundquist

A new triphenylethylene compound, Fc-1157a

SummaryThe basic pharmacological and biochemical properties of a new antiestrogen, Fc-1157a, are described. Fc-1157a is bound specifically and with high affinity to estrogen receptors. The binding is competitive with estradiol. Fc-1157a treatment induces translocation of estrogen receptors from cytoplasm to nucleus. The turnover rate of nuclear estrogen receptors is markedly lower than with estradiol, but is more rapid than after tamoxifen.Fc-1157a is an almost pure antiestrogen in rat uterus, but has intrinsic estrogenic activity in mouse uterus. In animal experiments Fc-1157a has shown antitumor properties, which are described in the companion paper.

Antihypertensive effects of practolol and sotalol

Practolol and sotalol were found to differ qualitatively in their effects on blood pressure (BP). The reductions in both systolic and diastolic BP and in heart rate were largely unrelated to differences in dosage and serum concentrations of practolol in 22 patients with mild‐to‐moderate hypertension. On the other hand, when due to sotalol, these effects were dose related in 12 patients. From 200 to 800 mg of both drugs were given daily in two doses. The differences from the posttreatment of placebo systolic/diastolic BP were at a maximum at 400 mg of practolol: 22/6, 18/9, and 18/6 mm Hg in a standing, sitting, and supine position. In 8 patients who tolerated 600 mg of sotalol, the differences were, respectively, 29/14, 22/18, and 27/18 mm Hg. Side effects with sotalol were numerous when the heart rate fell below the critical level of about 48. The highest tolerated serum concentration of sotalol was about 5.1 mg/1. A 600 mg dose of sotalol was tolerated as well and as often as 800 mg of practolol. The serum concentrations of both drugs were closely related to the dose per kilogram of body weight.

Pharmacokinetics of ftorafur after intravenous and oral administration

SummaryThe pharmacokinetics of ftorafur (FT), an antineoplastic agent, has been studied in seven cancer patients by determining concentrations of the unchanged compound in serum after single IV and PO doses of 2 g FT. Serum drug concentrations were determined by a new quantitative thin-layer chromatographic method. After IV administration, the mean half-lives of the distribution phase and elimination phase were 1.0 h and 7.6 h, respectively. Total serum clearance was 69 ml/h·kg and the apparent volume of distribution was 0.66 l/kg. Following PO administration there was a short lag-time, 11 min, before the appearance of FT in peripheral serum, and the maximum concentration in peripheral serum was achieved in 3.2 h. Oral absorption was complete and no significant first-pass metabolism could be observed. FT elimination, measured in serum taken from the portal vein and a peripheral vein, occurred substantially at the same rate after IV and PO administration. In contrast, after the PO dose FT appeared in the portal serum significantly earlier than in the peripheral serum, resulting in a difference of 1.7 h in the time of maximum serum concentration. This indicates fast gastrointestinal absorption of FT but hepatic retention (without metabolism) before the appearance of FT in the peripheral serum.

Effect of Trimethoprim on the Occurrence of Drug-Resistant Coliform Bacteria in the Faecal Flora

The occurrence of drug-resistant coliform bacteria was studied in the faecal flora of 30 persons receiving for 3 weeks either trimethoprim alone, a combination of sulphamethoxazole and trimethoprim, or a combination of sulphamethoxydiazine and sulphamethoxazole. Bacterial sensitivity was tested against trimethoprim, sulphamethoxazole-trimethoprim, sulphamethoxazole, and sulphaisodimidine. After treatment with trimethoprim alone, no increase in the occurrence of strains resistant to either trimethoprim or sulphonamides was observed. After treatment with sulphamethoxazole-trimethoprim, the faecal flora contained an increased percentage of sulphonamide-resistant coliforms but significantly less than found after treatment with sulphamethoxydiazine-sulphamethoxazole. In the persons receiving the sulphonamides only, a rapid increase in sulphonamide-resistant coliforms was observed. During the whole study, only one trimethoprim-resistant coliform strain was detected.