Benidipine hydrochloride--a new calcium-channel blocker of the dihydropyridine type. Pharmacokinetics, pharmacodynamics, tolerance and dose finding in mild to moderate hypertension.

(+/-)-(R*)-2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) is a newly synthetized calcium-channel blocker of the dihydropyridine type. In a phase I study with increasing single doses a statistically significant increase of the heart rate in supine and upright position as well as statistically significant decrease of the blood pressure in upright position was observed in healthy volunteers 1.5-6 h after application of 24 mg of KW-3049. Subsequently, in a placebo-controlled comparison in healthy volunteers the pulse rate in supine position increased statistically significantly on day 1 from 61.0 b/min (placebo) after application of 2 x 8 mg of KW-3049 to 67.4 b/min. After application of 2 x 10 mg of nifedipine the supine pulse rate increased to 63.3 b/min. The difference from placebo was not significant. At days 2-5 the pulse rate in upright position was always increased vs. placebo 3 h after application of KW-3049 and 1 h after application of nifedipine. As already observed in preclinical data, the mild onset of action with KW-3049 was also confirmed in these clinical phase I studies. Drug-induced effects on ergometric and psychomotoric parameters in healthy volunteers were mild, as expected, and due to aliquote dosages of 2 x 8 mg of KW-3049 and 2 x 10 mg of nifedipine only slightly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between sperm count, serum gonadotropins and testosterone levels in normo-, oligo- and azoospermia.

In 92 men with normozoospermia (greater than 40 X 10(6)/ml), 105 with slight oligozoospermia (greater than 10 X 10(6)/ml), 100 with severe oligozoospermia (less than 10 X 10(6)/ml) and 56 with azoospermia, serum testosterone, LH and FSH were measured radioimmunologically. With an increasing degree of reduction of spermatozoa, a decreasing testosterone level and increasing LH and FSH levels could be demonstrated. In normozoospermia, between 40 and 140 X 10(6)/ml, a direct correlation was found between FSH and sperm count, and, in the group between 40 and 100 X 10(6)/ml, a direct correlation between T and sperm count. A disturbed LH:T balance is often observed which beside decreased serum T levels demonstrates a testicular deficiency in androgen production.

Testosterone levels and gonadotrophins in Klinefelter's patients treated with injections of mesterolone cipionate.

Hormone levels were measured in patients with Klinefelter's syndrome after treatment with 100 mg mesterolone cipionate (twice monthly). There was no difference in plasma testosterone and FSH levels in treated and untreated patients. The basal and maximum LH levels were lower, but remained raised. The urinary excretion of testosterone as measured by liquid gaschromatography was higher in treated patients after treatment was discontinued.-From these results it is concluded that in spite of reported decreases of plasma testosterone during therapy with mesterolone cipionate this drug does not lead to severe impairment of the endogenous hormone production after discontinuing treatment.

Excretion of urinary testosterone in Klinefelter's syndrome.

The urinary testosterone excretion in 55 patients with Klinefelter's syndrome was determined by gas-chromatographic methods. The mean testosterone level in the group of Klinefelter patients was significantly decreased (15.7 mug/24 hrs) compared with the excretion by 30 normal men (44.1 mug/24 hrs). An age dependency of excretion levles was not obvious in chromatin-positive men when compared to healthy subjects. A correlation between testosterone excretion and configuration types seemed to be probable by reason of observations and statistical values. Average testosterone excretion increased with increasing normalization of body proportions. Gynecomastia was noticed in 56% of those examined. With increasing severity of gynecomastia the mean testosterone levels decreased. A correlation between beard and body hair, which was decreased in almost all subjects, and testosterone excreiton was not visible. With diminishing mean testosterone excretion an increase of osteoporosis seemed to be probable. A statistically significant difference was found when comparing patients who never had ejaculations with those who had regular libido and ejaculations. Klinefelter patients who had not succeeded in completing school or an occupational education showed a significantly decreased testosterone level as compared with others who had a profession.