Pharmacokinetic and pharmacodynamic comparison of subcutaneous versus intramuscular leuprolide acetate formulations in male subjects
| Autor: | Alex Yang, Raoul S. Concepcion, Stephan de la Motte, Judd W. Moul, Stuart Atkinson, Daniel Saltzstein, Neal D. Shore, E. David Crawford, Franklin Chu, John A. McLane |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
business.industry Urology 030232 urology & nephrology Cmax lcsh:Diseases of the genitourinary system. Urology lcsh:RC870-923 Serum luteinizing hormone 03 medical and health sciences 0302 clinical medicine Endocrinology Pharmacokinetics Leuprorelin 030220 oncology & carcinogenesis Internal medicine Pharmacodynamics medicine business Testosterone medicine.drug Original Research |
| Zdroj: | Therapeutic Advances in Urology, Vol 10 (2018) |
| Popis: | Background: The aim of this study was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of two distinct formulations of leuprolide acetate (LA); subcutaneous (SC) injection and intramuscular (IM) injection. Methods: A total of 32 healthy men were randomized to receive a single 7.5 mg injection of SC-LA ( n = 16) or IM-LA ( n = 16) in this phase I, open-label, parallel-group study. PK was assessed via LA concentrations, and PD via serum luteinizing hormone (LH) and testosterone (T) concentrations. Results: The initial surge of LA was higher for IM-LA than SC-LA (Cmax 27 ± 4.9 versus 19 ± 8.0 ng/ml, respectively), with a shorter tmax (1.0 ± 0.4 versus 2.1 ± 0.8 h). The duration of quantifiable LA concentration was longer for SC-LA (up to 56 versus 42 days for SC-LA and IM-LA, respectively). Median LH concentrations in both groups rapidly increased, followed by gradual decrease. However, SC-LA demonstrated a longer duration of LH suppression, with median levels remaining below 1.0 IU/l through Day 56 compared with IM-LA where LH started to rise by Day 35. Consequently, serum T began to increase by Day 42 in the IM-LA group, with only four subjects maintaining levels ⩽50 ng/dl, compared with 14 subjects in the SC-LA group. By Day 56, 13 SC-LA subjects maintained serum T levels ⩽50 ng/dl. Both SC-LA and IM-LA were well tolerated. Conclusions: Both formulations demonstrated consistent delivery of drug over 1 month; however, SC-LA provided a longer duration of action than expected based on the dosing interval. This profile suggests that SC-LA will provide effective suppression of T over a longer period of time, permitting greater injection scheduling flexibility. |
| Databáze: | OpenAIRE |
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