Pharmacokinetics of pengitoxin and its therapeutic efficacy in congestive heart failure.

In a therapeutic study, 120 inpatients suffering from congestive heart failure were treated with a daily maintenance dose of 0.3 mg pengitoxin (penta-acetyl-gitoxin) over several weeks or months. The plasma level and the glycoside concentration in urine were measured by radioimmunoassay. The therapeutic effects were evaluated considering clinical signs and criteria following the functional capacity according to the New York Heart Association (NYHA). In 27 patients both plasma and urine concentration were measured during 2 weeks after the beginning of the pengitoxin therapy. On the 3rd day of the pengitoxin dosage schedule, a mean plasma level of 18.1 ng.ml-1 (SD 5.1 ng.ml-1) was measured. During this day 26.6% of the daily administered glycoside dose was excreted in urine. In 26 of the 120 patients the mean steady state plasma level was between 7.6 and 22.5 ng.ml-1. A maximum of frequency was found in the 17.6 to 22.5 ng-subclass. In 118 patients the mean urinary excretion of 16-acetyl-gitoxin reached 24.7% (SD 11.8%) of the administered dose. The creatinine clearance and the 16-acetyl-gitoxin plasma level did not correlate, while between the renal clearance values of creatinine and the glycoside a correlation was found, however, it was of no significance for dosage schedules in patients with impaired renal function. After treatment, the NYHA classes III and II were reached in 57 patients; in 3 patients suffering from renal diseases, the NYHA class I remained unchanged. In 90 patients the clinical signs improved and in 27 patients the clinical situation remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Elimination of 16-acetyl-gitoxin in patients suffering from impaired liver function.

In ten patients suffering from moderate to severe disturbances of liver function (hepatic cirrhosis, carcinomatous metastases of the liver) the elimination of 16-acetyl-gitoxin from plasma was measured after a single oral dose of 1.2 mg pengitoxin. In 9 of 10 patients the mean half-life amounted to 67.3 h (SD 14.2 h). In one patient with carcinomatous infiltration of the liver and concomitant cirrhosis, the half-life was prolonged to 165.3 h. The results point to an unchanged elimination of 16-acetyl-gitoxin in patients suffering from liver cirrhosis.

[Effects of menopause, pregnancies, breast feeding and hormonal contraceptives on the course of rheumatoid arthritis]. / Beeinflussung durch Klimakterium, Schwangerschaften, Stillperioden und Ovulationshemmer.

PIP: Of 763 patients who were treated for rheumatoid arthritis (RA), 219 went through menopause, 114 were pregnant, 92 breast-fed children, and 29 used oral contraceptives. Of the 219 menopausal women, 5% experienced an improvement and 46.1% an adverse effect on the RA. It was found that those who experienced improvement during menopause more often had had RA for longer periods and tended to have developed RA before the 45th year of age. 59 patients first developed RA during the menopause, and a general adverse effect of menopause on RA was observed. Increased seronegativity and a reduction in rheumafactor levels were observed in this group, as well as a significantly higher BSG level. In the group which developed RA during menopause, increases in morphological stage II, in grade I of functional inefficiency, and in grip strength and the BFT were observed. There was also a significant increase in the incidence of long arthralgic periods before developing RA during menopause. The relationship between RA during menopause and various other factors, e.g. occupation, weight, prior therapy, is also discussed. Among the 114 pregnant patients, 42 reported a positive effect and 30 an adverse effect on RA. Among the 92 patients who breast-fed their children, 25 reported an adverse effect and 19 reported improvement of RA. Patients who had had RA for longer periods more often reported improvement during pregnancy and breast feeding. Adverse effects of pregnancy on RA usually continued during the breast feeding period. Of the 29 patients who had used oral contraceptives, 5 reported a positive effect on RA.^ieng