Dataset Information

Pharmacokinetic and pharmacodynamic comparison of subcutaneous versus intramuscular leuprolide acetate formulations in male subjects.

ABSTRACT:

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 (C_max 27 ± 4.9 versus 19 ± 8.0 ng/ml, respectively), with a shorter t_max (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.

SUBMITTER: Saltzstein D

PROVIDER: S-EPMC5805007 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

Pharmacokinetic and pharmacodynamic comparison of subcutaneous <i>versus</i> intramuscular leuprolide acetate formulations in male subjects.

Saltzstein Daniel D Shore Neal D ND Moul Judd W JW Chu Franklin F Concepcion Raoul R de la Motte Stephan S McLane John A JA Atkinson Stuart S Yang Alex A Crawford E David ED

Therapeutic advances in urology 20171122 2

<h4>Background</h4>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.<h4>Methods</h4>A total of 32 healthy men were randomized to receive a single 7.5 mg injection of SC-LA (<i>n</i> = 16) or IM-LA (<i>n</i> = 16) in this phase I, open-label, parallel-group study. PK was assessed <i>via</i> LA concentrations, and PD <i>via</i> serum luteiniz ...[more]

PMID: 29434672

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