A RANDOMIZED 3-WAY CROSS-OVER STUDY IN HEALTHY PITUITARY-SUPPRESSED WOMEN TO COMPARE THE BIOAVAILABILITY OF HUMAN CHORIONIC-GONADOTROPIN (PREGNYL(R)) AFTER INTRAMUSCULAR AND SUBCUTANEOUS ADMINISTRATION

The objective of this study was to compare the bioavailability of s.c. and i.m. administration of human chorionic gonadotrophin (HCG; Pregny l(R)), In a randomized, single-centre, three-way cross-over study, 18 healthy pituitary-suppressed volunteers were assigned to single HCG in jections of 5000 and 10 000 IU i.m. and 10 000 IU s.c. Rate (C-max, t( max)) and extent [area under curve from zero to infinity (AUC(0-infini ty))] of absorption of HCG were determined. Serum immunoactive HCG inc reased from 0.4-0.5 IU/l at baseline to mean peak concentrations, whic h were reached 20 h after injection of 156 IU/l with 5000 IU i.m., of 307 IU/l with 10 000 IU i.m. and of 339 IU/l with 10 000 IU s.c. Eight days after administration, <10% of the maximum HCG activity was found for each regimen. The elimination half-life (t(1/2)) was on average 3 2-33 h, irrespective of the treatment regimen. Intramuscular and s.c. injections of 10 000 IU HCG were bioequivalent with respect to AUC(0-i nfinity). The C-max and t(max) were also similar between the two admin istration routes but bioequivalence could not be proven due to intersu bject variability. Intramuscular doses of 5000 IU and 10 000 IU HCG we re dose-proportional. Since s.c. HCG is bioequivalent to i.m. HCG with respect to extent of absorption (its major pharmacokinetic variable) and is well tolerated, the s.c. administration route may be effectivel y and safely used in assisted reproduction. Moreover, since s.c. injec tion can be performed by the patients themselves, acceptability may be enhanced.