Biomedical subjects

T R Tice

Publications and source records attributed to T R Tice.

22 records · Page 2Linked to original sources

PubMed1983

Clinical evaluation of an improved injectable microcapsule contraceptive system.

Pharmacokinetics and pharmacodynamics of a long-acting injectable microcapsule, poly(DL-lactide-co-glycolide), delivery system were tested in 10 women. Two doses (75 or 100 mg of norethindrone) were administered by intramuscular injection. Treatment suppressed ovarian function and inhibited ovulation for 3 months in all subjects. Levels of norethindrone in subjects who received the 100 mg dose were proportionately higher than those in subjects who received the 75 mg dose. Subsequent to the injection, there was a rapid rise in the serum levels of norethindrone followed by a gradual decline until 8 to 10 weeks. Between 10 and 20 weeks after treatment, there was a secondary rise and fall in the serum levels of norethindrone. Treatment caused suppression of the endometrium for 3 months, and, except for spotting and irregular menstrual cycles, there were no adverse side effects. Treatment had no significant effect on serum lipids.

Adult↗

PubMed1983

Poly(DL-lactide-co-glycolide)/norethisterone microcapsules: an injectable biodegradable contraceptive.

Microcapsules made from a biocompatible, biodegradable polymeric excipient, poly(DL-lactide-co-glycolide) (DL-PLGA) that contained 22 weight percent (wt %) norethisterone (NET), were prepared by a solvent-evaporation microencapsulation process. The effects of changing both the lactide-to-glycolide ratio of the DL-PLGA and the size of the microcapsules on the rate of NET release and the rate of excipient biodegradation were determined in vivo. NET release rates were determined in baboons after injecting the microcapsule formulations intramuscularly. Serum samples obtained at various times following treatment were analyzed for NET, progesterone, and estrogen by radioimmunoassay (RIA). Biodegradation kinetics were determined by injecting NET microcapsules made from radiolabeled DL-PLGA intramuscularly into the hind legs of rats. Residual radioactivity at the injection site was determined at various times after treatment by combustion analysis of the muscle tissue. Changing the ratio of the comonomers to include more glycolide (DL-lactide:glycolide-96:4, 92:8, 87:13, 74:26) increased the rate of NET release and accelerated the biodegradation of the copolymer excipient. Decreasing the size of the microcapsules increased the rate of NET release. On the basis of these studies a NET microcapsule formulation has been identified for clinical testing which releases NET for 3 months and biodegrades completely within 6 months.

Animals↗

PubMedDate not supplied

Prolonged suppression of plasma LH levels in male rats after a single injection of an LH-RH agonist in poly(DL-lactide-co-glycolide) microcapsules.

The authors have examined the effects of a subcutaneous injection of the LH-RH agonist D-Trp6-LH-RH formulated in biodegradable poly(DL-lactide-co-glycolide) microcapsules on plasma levels of D-Trp6LH-RH, LH, and PRL in adult, gonadectomized male rats. Immunoreactive D-Trp6-LH-RH was detectable in the plasma of these animals at 1, 2, 3, and 4 weeks after injection. LH concentrations were greatly reduced 1 week after administering the D-Trp6-LH-RH microcapsule, continued to decrease during the following week, and remained suppressed until the end of the study, 6 weeks after the injection. Plasma PRL levels appeared elevated 1 to 2 weeks after the injection and suppressed thereafter, but these effects were significant only in animals rendered hyperprolactinemic by transplantation of an isologous pituitary under the renal capsule. These results demonstrate that an LH-RH agonist formulated in biodegradable microcapsules and administered as a subcutaneous injection can exert marked biologic effects in rats for at least 6 weeks. These findings also suggest that prolonged exposure to an LH-RH agonist may first produce stimulation, followed by an inhibition of PRL release from both in situ and ectopic pituitaries.

Animals↗

PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of a parenteral testosterone microsphere formulation in the male rat. Demonstration of dose dependence and controlled release.

This study examined the pharmacokinetics (the time course and pattern of testosterone release) and pharmacodynamics (effects on accessory sex organ weights, and serum LH and FSH levels) of a biodegradable testosterone microsphere formulation in the male rat. Two hundred seventy-five 55-day-old, sexually mature male rats underwent surgical orchiectomy or sham surgery and were divided into five groups as follows, to receive placebo or testosterone microsphere systems designed to release 25, 75, or 225 micrograms/day testosterone: group I: intact age-matched controls, sham operated, placebo microspheres; group II: surgically orchiectomized, placebo microspheres; group III: surgically orchiectomized, 25 micrograms/day testosterone microspheres; group IV: surgically orchiectomized, 75 micrograms/day testosterone microspheres; and group V: surgically orchiectomized, 225 micrograms/day testosterone microspheres. Serum testosterone levels were fairly uniform from day 2 to 85 without any significant trend. After day 100, serum testosterone levels gradually fell into the castrate range by day 196. There was a dose-dependent increase in serum testosterone levels in groups III, IV, and V over those seen in group II (castrated rats, placebo treated). Prostate and seminal vesicle weights were significantly lower in castrated animals treated with placebo or the 25-micrograms/day testosterone microsphere system (group III). Mean prostate and seminal vesicle weights in groups IV and V were not significantly different from those in intact controls (group I) in the first 85 days. After day 85-100, seminal vesicle and prostate weights declined gradually in groups III, IV, and V, approaching castrate range by day 196.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗