Studies on Pharmacokinetics of STS 557 in Animal Species and Man

Abstract

Following oral and i.v. administration of [14 alpha, 15 alpha-3H]-STS 557 to beagle dogs, baboons, rats and female volunteers, plasma level courses of total radioactivity and STS 557, and radioactivity excretion in urine and feces have been investigated. Bioavailability of orally administered STS 557 was found to be 80--90% in man and beagle dog, 70--80% in baboon and rat. Concerning the systemic availability following oral administration of equivalent doses, the following order was established: beagle dog greater than man greater than baboon greater than rat. Equilibrium dialysis indicates species differences in plasma protein binding and a considerable part of STS 557 to be present in plasma unbound. STS 557 is rather rapidly eliminated from the plasma compartment of all species investigated with half lives less than or equal to 10 h. As an additional time parameter of pharmacokinetics the "mean residence time" was used. Urinary excretion of STS 557 metabolites is dominant in all species, including the rat. In contrast to the great part of STS 557 in plasma total radioactivity, only small amounts of unchanged STS 557 are excreted in urine. First results of current studies in rabbits are presented, too.

Studies on the Biotransformation of the Progestagen Dienogest in the Rabbit *)

“…In the CH2Cl2 extract from plasma Dienogest is the main constituent. This knowledge was valuable in the development of a radioimmunoassay for this compound (Do Khac lieu et al, 1986;lobe et al, 1986). Separation by HPLC of a toluene extract from rabbit plasma following administration of 311-Dienogest gave also evidence that Dienogest is the main compound in the toluene-extractable fraction (TEF) (Wehrberger et al, 1985) and that an approximate determination of Dienogest by toluene extraction of plasma is possible (Hillesheim et al, in press).…”

Biotransformation of Current-Use Progestin Dienogest and Drospirenone in Laboratory-Scale Activated Sludge Systems Forms High-Yield Products with Altered Endocrine Activity

“…Although TP bioactivities were not evaluated explicitly here, this information was sometimes available from the literature. For example, aromatic TP 309 and TP 311 of DIE were previously identified as DIE metabolites in microbes, mammals, and humans and minor photoproducts. ,− A-ring aromatization implies biotransformation of the progestogenic DIE into estrogenic TPs (Figure ). Notably, both TP 309 and TP 311 exhibit estrogen receptor binding activities ∼30% of those of 17β-estradiol, , similar to those observed for estrone.…”