Sustained-release hormonal preparations XV: release of progesterone from cholesterol pellets in vivo.
Progesterone-sterol pellets were made that porvided a zero-order release of progesterone for 80 days. 4-(14)C-Progesterone was used to measure the release in vitro and in vivo. The dissolution rate in vitro (distilled water as the desorbing medium) for progesterone-cholesterol (59:41 w/w) and the progesterone-beta-sitosterol (47:53 w/w) pellets was 72 microng/100 mm2/24 hr. The average in vivo absorption from subcutaneously implanted pellets in rabbits was 2 +/- 0.1 microng/ml of plasma/cm2 of surface area. Of this amount, 20-25% was progesterone; the remainder was progesterone metabolites and conjugates. Zero-order release (plasma levels) was obtained for approximately 80 days or until about 70% of the available progesterone was exhausted. During this time, the level of excreted radioactivity in urine continuously decreased, indicating that monitoring only this parameter would lead to erroneous conclusions. A long-term effect and increased effectiveness were obtained with a 5-20-mg progesterone equivalent dose, using gel prepared from 2% methylcellulose as the suspending medium.
D000818:Animals; D002369:Castration; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol; D004343:Drug Implants; D005260:Female; D008863:Microspheres; D010060:Ovulation / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects; D011374:Progesterone / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D012995:Solubility; D013997:Time Factors; D014867:Water
D004343:Drug Implants; D014867:Water; D011374:Progesterone; D002784:Cholesterol