Fred A. Kincl

Sustained release hormonal preparations: 3. Biological effectiveness of 6-methyl-17α-acetoxypregna-4,6-diene-3,20-dione

Abstract Biological activity of 6-methyl-17 α -acetoxypregna-4,6-diene-3,20-dione was compared using three different routes of administration: subcutaneous injection, gavage and dimethylpolysiloxane implant. The implant provided the most efficacious way to administer this steroid: from 6 to 25 times less was needed to produce comparable biological effects.

Sustained release hormonal preparations: 2. Factors controlling the diffusion of steroids through dimethylpolysiloxane membranes

Abstract Mean diffusion of 6-methyl-16-methylene-17 α -acetoxypregna-4, 6-diene-3, 20-dione through dimethylpolysiloxane membrane into water was 140 μg/24 hrs/100 mm 2 /0.1 mm; (dl)-13β-ethyl-17 α -ethynyl-17β-hydroxygon-4-en-3-one diffused with a rate of 73 μg/24 hrs/100 mm 2 /0.1 mm. When plasma instead of water was used for incubation, the diffusion rates were increased by the following factors: 2.4 times for 19-norpregn-4-ene-3, 20-dione; 1.5 times for 6-methyl-17 α -acetoxypregna-4, 6-diene-3, 20-dione, and 4.7 times for (dl)-13β-ethyl-17 α -ethynyl-17β-hydroxygon-4-en-3-one. Measurements of diffusion through porous glass discs, and of solubility in different solvents indicated that the steroid molecules diffuse through the dimethylpolysiloxane in a non-solvated form.

Testosterone plasma levels in adult male rats injected neonatally with estradiol benzoate or testosterone propionate.

Abstract Peripheral testosterone plasma levels of 240 day old rats, determined by competitive protein binding method, were 504 mμg/100 ml of plasma. In males of the same age, injected at the age of 5 days with 50 or 250 μg of estradiol benzoate, the mean values were 270 mμg and 195 mμg respectively. Neonatal injection of 250 μg of testosterone propionate produced no change in circulating testosterone levels; mean value for this group was 525 mμg.

Sustained release hormonal preparations. 6. Permeability constant of various steroids.

Permeation of 6-methyl-17α-acetoxy-4,6-pregnadiene-3,20-dione through polydimethylsiloxane rubber film (PDS) was measured for several thicknesses and areas and was shown to follow Ficks law. The permeability constant for this steroid was 3.91 ± 0.25 × 10−2cm2/hr. From less extensive experimental data the permeability constant was calculated also for a number of other steroids. This constant can be used to estimate amounts of steroids diffusing from cylindrical implants. Relative diffusivity was measured for cylindrical implants filled with dry, crystalline steroids and with steroids suspended in oil or liquid polytrifluropropylmethylsiloxane; the rates were higher when no suspending media were used.

Neonatal sterilization of rodents with steroid hormones: 3. Influence of neonatal treatment with testosterone propionate or estradiol benzoate on steroids in plasma of adult male rats

Abstract The influence of neonatal estrogen or androgen treatment was compared in adult male rats by measuring disappearance of testosterone, 4-androstene-3,17-dione, 3β-hydroxy-5-androsten-17-one and 3β-hydroxy-5-pregnen-20-one from plasma. It was found that neonatal treatment with estradiol benzoate altered the rate of transformation of testosterone in plasma when measured 20 min after intravenous injection; the relative specific activity of β-hydroxy-5-pregnen-20-one and β-hydroxy-5-androsten-17-one was apparently decreased, whereas that of testosterone and androstenedione was increased.

Sustained release hormonal preparations 12. Plasma levels of 6-methyl-17α-acetoxy-4,6-pregnadiene-3,20-dione in hamsters

Abstract Absorption of 6-methyl-17α-acetoxy-4,6-pregnadiene-3,20-dione from polydimethylsiloxane implants in hamsters was monitored by measuring peripheral plasma levels and excretion in urine and feces. The absorption was time dependent. Mean values 24 hrs after implantation were 684 ng (plasma volume based on 4.1% of body weight); this rose to 2876 ng on day 7 after insertion. Similarly, total excretion rose from a mean value of 5282 ng/24 hrs on day 1 to 15483 ng/24 hrs on day 7.

The Influence of Thymectomy and Steroid Hormones in Neonatal Rats

Summary Extirpation of thymus within 24 hr after birth increased the sensitivity of rats to steroid hormones injected at the age of 5 days. In 56-day-old males the atrophy of testis and of accessory sex tissues produced by a single injection of estradiol benzoate was more severe in thymectomized animals than in sham-operated controls. In female rats the atrophy produced by injecting the same steroid resulted in greater atrophy of the uterus in thymectomized animals than in controls.

Sustained release hormonal preparations: X. Uptake of 6-methyl-17α-acetoxy-4,6-pregnadiene-3, 20-dione released from polydimethylsiloxane implants by various tissues of male and female rats

Abstract Plasma levels and uptake by various tissues of 6-methyl-17α-acetoxy-4,6-pregnadiene-3,20-dione and metabolites released from polydimethylsiloxane implants were compared in female and male rats. In females circulating levels 4 days after implantation were 3120 ng 100 ml of plasma; in males the corresponding value was 2790 ng 100ml . The uptake by the hypothalamus, cerebellum, pituitary, adrenals, liver and body fat was higher in female animals than in male animals. Estrone treatment of males influenced uptake in the liver, adrenals and fat but not in the other organs.