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A randomized three-way cross-over study in healthy pituitary-suppressed women to compare the bioavailability of human chorionic gonadotrophin (Pregnyl®) after intramuscular and subcutaneous administration

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Author: Mannaerts, B.M.J.L. · Geurts, T.B.P. · Odink, J.
Type:article
Date:1998
Institution: Centraal Instituut voor Voedingsonderzoek TNO
Source:Human Reproduction, 6, 13, 1461-1464
Identifier: 234542
doi: DOI:10.1093/humrep/13.6.1461
Keywords: Nutrition · Bioequivalence · Human chorionic gonadotrophin · Intramuscular · Pharmacokinetics · Subcutaneous · Chorionic gonadotropin · Adult · Area under the curve · Bioequivalence · Clinical trial · Controlled study · Dose response · Drug absorption · Drug bioavailability · Drug blood level · Drug elimination · Drug half life · Female · Human · Human experiment · Hypopituitarism · Intramuscular drug administration · Normal human · Randomized controlled trial · Subcutaneous drug administration · Administration, Oral · Adolescent · Adult · Chorionic Gonadotropin · Contraceptives, Oral · Cross-Over Studies · Dose-Response Relationship, Drug · Female · Humans · Injections, Intramuscular · Pituitary Gland

Abstract

The objective of this study was to compare the bioavailability of s.c. and i.m. administration of human chorionic gonadotrophin (HCG; Pregnyl®). In a randomized, single centre, three-way cross-over study, 18 healthy pituitary-suppressed volunteers were assigned to single HCG injections of 5000 and 10000 IU i.m. and 10000 IU s.c. Rate (C(max), t(max)) and extent [area under curve from zero to infinity (AUC(o-∞))] of absorption of HCG were determined, Serum immunoactive HCG increased from 0.4-0.5 IU/l at baseline to mean peak concentrations, which were reached 20 h after injection of 156 IU/l with 5000 IU i.m., of 307 IU/l with 10000 IU i.m. and of 339 IU/l with 10000 IU s.c. Eight days after administration, < 10% of the maximum HCG activity was found for each regimen. The elimination half-life (t( 1/4 )) was on average 32-33 h, irrespective of the treatment regimen. Intramuscular and s.c. injections of 10000 IU HCG were bioequivalent with respect to AUC(0-∞). The C(max) and t(max) were also similar between the two administration routes but bioequivalence could not be proven due to intersubject variability. Intramuscular doses of 5000 IU and 10000 IU HCG were 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 effectively and safely used in assisted reproduction. Moreover, since s.c. injection can be performed by the patients themselves, acceptability may be enhanced.