The pharmacokinetics of 3-keto-desogestrel and ethinyl estradiol (EE) and the safety of Org5187 (150 mcg desogestrel and 30 mcg EE) in 17 healthy Japanese women (single dose--8, multiple dose--9) were studied after oral administration. After single dose administration, Tmax, Cmax elimination 1/2 life (t1/2beta), and the area under the curve (AUC) of 3-keto-desogestrel were 1.8 +or- 0, 7 hour; 3.9 +or- 1.36 pmol/ml, 19.1 +or- 13.0 hours; and 28.6 +or- 22.9 pmol h/ml, respectively. On the other hand, those after multiple dose were 1.2 +or- 0.6 hour (Tmax), 12.12 +or- 5.49 pmol/ml (Cmax), 22.0 +or- 9.6 hour (t1/2beta), and 97.2 +or- 36.8 pmol h/ml (AUC), respectively. Pharmacokinetic parameters of EE were 1.69 +or- ), 96 hour (Tmax), 0.638 +or-0.025 pmol/ml (Cmax), 20.0 +or- 12.3 hour (t1/2beta), and 7.0 +or- 4.12 pmol h/ml (AUC) after single dose, and 1.11 +or- 0.5 (Tmax), 1.180 +or- 0, 315 pmol/ml (Cmax), 23.7 +or- 8.8 hour (t1/2beta), 11.7 +or- 3, 3pmol h/ml (AUC) after multiple dose. The serum concentrations of 3-keto-desogestrel and EE reached a steady state on the 15th day after initiating administration. No differences were observed between Japanese and European female volunteers in the pharmacokinetics of 3-keto-desogestrel and EE. During the period of multiple dose treatment, neither irregular bleedings nor side effects leading to dropouts were observed. (author's)
To examine a change occurring in the coagulation-fibrinolytic system during oral contraceptive (OC) administration, the author measured fibrinopeptide A and Bbeta15-42 (FPA and FPBbeta15-42) over a long period of time. These are sensitive indicators of coagulation and fibrinolytic activity as well as coagulation fibrinolysis inhibiting factor plasma antithrombin III (AT III) and alpha2 plasmin inhibitor (alpha2 PI). The interesting results are listed as follows. 1) FPA showed almost no change during OC administration, nor was thrombin observed to have been produced. 2) FPB15-42 increased when the drug was administered 3-5 times and 11-12 times (p0.05) but showed significant difference when the drug was administered for the 18th and 24th times. 3) Plasma AT III activity decreased significantly (p0.05) when the drug was given for the 1st time but showed no change when the drug was administered 3-5 times. When administered 11-12 times, AT III was observed to decrease again, but repeat administrations did not cause AT III to decline; this was probably due to inurement. A similar change in immune activity concentration was observed but the change was slight. 4) When the drug was given 3-5 times following the 1st administration, a slight decrease (p0.1) occurred in alpha2 PI levels, but no change worth of mention was noted to occur thereafter. 5) In patients who received norethisterone 5 mg alone, no particular change was seen to occur in FPA, FPBbeta15-42, AT III, or alpha2 PI. Judging from the above results, especially that there was an increase in FPA, the decrease in AT III levels may be attributed not to a reduction in consumption but to a decrease in the AT III itself, due to estrogens. It is possible also that an increase in FPBbeta 15-42 led to plasmin production which was the reason so few thromboses were observed to form. (author's modified)
The effects of menfegol-coated condoms on sperm motility and viability were investigated. At 0.5 mg/ml and higher concentrations, mennfegol, a spermicidal agent, was found not only to suppress sperm motility buy also to kill the sperm completely, indicating that it has strong spermicidal potency. Normal semen samples were ejaculated directly into menfegol-coated or uncoated condoms. The sperm motility and viability were examined immediately after ejaculation. In the menfegol-coated condom, sperm motility was completely suppressed and no viable sperm were observed, whereas in the uncoated condom, most of the sperm were still alive, although their motility was virtually or completely suppressed. These results indicate that the menefegol-coated condom provides a new birth control method which enhances contraceptive efficacy with added spermicidal activity. (author's)
Early abortion traditionally referred to abortion within 12 weeks of gestational age, but it is necessary to divide it into 3 stages: ultra early abortion for the one within 5 weeks of gestational age; very early abortion for the one within 8 weeks; early abortion for the one between 8 and 12 weeks. Progress and development in them are of IVF-ET and GIFT necessitated redefining pregnancy and resulted in great number of terms related to early pregnancy and abortion, which are not standardized and sometimes confusing. In connection with IVF-ET research, the following 3 stages of early pregnancy are recognized by Japanese doctors. Biochemical pregnancy is when plasma level of beta HCG is above norm. Early clinical pregnancy is when the Gestational sac is detected by ultrasonography but the heat beat of fetus is not yet confirmed. Established clinical pregnancy is when the heart beat of the fetus is confirmed via ultrasonography. Early abortion is divided into 2 stages: subclinical abortion (menstrual abortion), which is menstrual like fetus wastage in biomedical pregnancy, and clinical abortion in which a blighted ovum is detected by ultrasonic examination. Classification above is simple and easy but it heavily relies on measurement methods, results of which often fluctuate and are subject to change. It seems desirable to classify early abortion according to gestational age (GS). GS may be detected as early as 4 weeks, is above 10 mm in the maximum diameter at 5 weeks, and is detected in all cases at 6 weeks. Human chorionic gonadotropin (HCG) test by 1000 IU/1 sees positive response in almost all cases at 6 weeks, while HCG by 200 IU/1 sees the same at 5 weeks. The heart beat of the fetus is believed to commence at 4 weeks but it is not detected by ultrasonography at the earliest till the end of 5 weeks and in all cases till 8 weeks. The classification of ultra early abortion, very early abortion and early abortion, is based on above findings.
LDH-C4 is a specific isoenzyme, distinct from other LDH isoenzymes with regard to its locality and kinetic properties. Because about 80% of LDH in spermatozoa contains LDH-C4, it must be strongly related to very specific metabolic processes connected with sperm. In order to investigate the mechanism of action of gossypol, which is a new male contraceptive, the effects of gossypol on LDH-C4 were examined. LDH-C4 from human seminal plasma was purified by Oxamate-Sepharose 4B affinity column chromatography and AMP affinity column chromatography. The homogeneity of LDH-C4 was proved by agar gel electrophoresis and polyacrylamide disc gel electrophoresis. Gossypol was dissolved in 95% ethanol. LDH activity was analyzed spectrophotometrically. The cuvette contained 0.1 M PBS (pH 7.4), 0.2 mM pyruvate, and 0.115 mM NADH. Gossypol was added to give a final concentration of between 1 x 10 -6 M and 1 x 10 -4 M. Ethanol did not inhibit LDH-C4 activity, but gossypol did inhibit it in a dose-dependent manner when tested at a concentration of 5 x 10 -6 M, 1 x 10 -5 M, 5 x 10 -5 M, and 1 x 10 -4 M. (author's modified)
