Pharmacokinetics of recombinant human luteinizing hormone after intravenous, intramuscular, and subcutaneous administration in monkeys and comparison with intravenous administration of pituitary human luteinizing hormone
| Autor: | G Zanolo, H C Porchet, J Y Le Cotonnec, B. Neuteboom, S Canali |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Pituitary gland medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism Injections Subcutaneous Clinical Biochemistry Cmax Biochemistry Injections Intramuscular Antibodies Drug Administration Schedule Route of administration Endocrinology Bolus (medicine) Pharmacokinetics Internal medicine medicine Animals Dose-Response Relationship Drug business.industry Biochemistry (medical) Luteinizing Hormone Recombinant Proteins Macaca fascicularis medicine.anatomical_structure Pituitary Gland Injections Intravenous Gonadotropin business Luteinizing hormone Intramuscular injection Half-Life |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 80(2) |
| ISSN: | 0021-972X |
| Popis: | To assess the pharmacokinetics of recombinant human LH (rhLH) in monkeys, we measured serum LH levels after single iv injection and after single and repeated doses by the im or sc route. A single iv bolus of 400 IU/kg rhLH or pituitary hLH (phLH) in six cynomolgus monkeys resulted in parallel concentration-time curves. The initial and terminal half-lives of rhLH (0.8 and 11 h) were comparable to those of phLH (0.6 and 10 h). The serum levels of phLH were consistently higher due to the fact that the immunological dose of phLH was higher. Administration of increasing iv doses of rhLH (10, 63, and 400 IU/kg) to six monkeys showed that the pharmacokinetics are linear over this dose range. The total clearance for the two higher doses was 0.03 L/h.kg. Systemic bioavailability was 50% after a single sc injection of 400 IU/kg and 61% after a single im injection of the same dose. The peak concentration (180 IU/L) after im injection was reached after 2.7 h. This was higher and sooner than after sc injection (110 IU/L after 5.3 h). The terminal half-life by both routes was similar to that seen after iv injection (11 h). Daily sc or im administration of 63 IU/kg for 7 days confirmed these findings. There was no accumulation of rhLH. Some monkeys developed antibodies, especially after repeated administration. They were excluded from the analysis. No significant local or systemic adverse events occurred. |
| Databáze: | OpenAIRE |
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