Daniel Saltzstein1, Neal D Shore2, Judd W Moul3, Franklin Chu4, Raoul Concepcion5, Stephan de la Motte6, John A McLane7, Stuart Atkinson8, Alex Yang8, E David Crawford9. 1. Urology San Antonio, 18139 Meisner Drive San Antonio, TX 78258 USA. 2. Carolina Urologic Research Center, Myrtle Beach, SC, USA. 3. Division of Urology, Duke University, Durham, NC, USA. 4. San Bernardino Urology, San Bernardino, CA, USA. 5. The Comprehensive Prostate Center, Nashville, TN, USA. 6. SynteractHCR Deutschland GmbH, Munich, Germany. 7. TOLMAR Inc., Fort Collins, CO, USA. 8. TOLMAR Pharmaceuticals Inc., Lincolnshire, IL, USA. 9. University of Colorado at Denver, CO, USA.
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 (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.
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.
Authors: Oliver Sartor; Martin K Dineen; Ramon Perez-Marreno; Franklin M Chu; Graham J Carron; Robert C Tyler Journal: Urology Date: 2003-08 Impact factor: 2.649
Authors: Franklin M Chu; Maury Jayson; Martin K Dineen; Ramon Perez; Richard Harkaway; Robert C Tyler Journal: J Urol Date: 2002-09 Impact factor: 7.450
Authors: E David Crawford; Axel Heidenreich; Nathan Lawrentschuk; Bertrand Tombal; Antonio C L Pompeo; Arturo Mendoza-Valdes; Kurt Miller; Frans M J Debruyne; Laurence Klotz Journal: Prostate Cancer Prostatic Dis Date: 2018-08-21 Impact factor: 5.554