Transdermal absorption of the progestin ST-1435: therapeutic serum steroid concentrations and high excretion of the steroid in saliva.
The synthetic progestin ST-1435 was administered transdermally to six healthy women during the late luteal phase. The steroid was applied to the periumbilical area in a commercial gel ("Progestogel"), also containing progesterone. Single doses of 2.3, 4.5 and 9.0 mg of ST-1435 were given in three experiments and repeated doses of 2.3 mg of ST-1435 for five days were given in another three experiments. Samples of serum and saliva were collected and the concentrations of ST-1435 and progesterone were determined by radioimmunoassays. Transdermal absorption of the synthetic progestin ST-1435 was shown to result in serum steroid concentrations high enough for therapeutic purposes. The concentration of ST-1435 in serum was still high 24 hours after application, reflecting sustained release of the steroid from the skin. In the five-day experiments, relatively constant serum levels were achieved in different individuals, and a single dose per day seems sufficient. High excretion of ST-1435 in saliva was found two hours after gel application. However, the concentrations of serum and salivary ST-1435 were not directly correlated in different individuals. Transdermal application of ST-1435 might offer a good alternative for systemic progestin treatment.
Haukkamaa
M
M
Department of Medical Chemistry, University of Helsinki, Finland.
Laurikka-Routti
M
M
Heikinheimo
O
O
D000279:Administration, Cutaneous; D002852:Chromatography, Ion Exchange; D002855:Chromatography, Thin Layer; D003271:Contraceptive Agents, Female; D004305:Dose-Response Relationship, Drug; D005260:Female; D005782:Gels; D006801:Humans; D009653:Norprogesterones / Q000097:blood / Q000493:pharmacokinetics*; D011863:Radioimmunoassay; D012044:Regression Analysis; D012463:Saliva / Q000737:chemistry*; D012869:Skin Absorption; D013997:Time Factors
D003271:Contraceptive Agents, Female; D005782:Gels; D009653:Norprogesterones; C029167:ST 1435