Oxandrolone Coadministration Does Not Alter Plasma Propranolol Concentrations in Severely Burned Pediatric Patients.

"This study was supported by NIDILRR (90DP0043-02-01 [DNH]), National Institutes of Health (P50GM060338, R01GM056687, and T32GM008256 [DNH]; R01HD049471 [OES]; and R01GM112936 [CCF]), and Shriners of North America (84080, 79135, 80100, and 71008 [DNH]; 71009 [OES]; and 84291 [CCF]). This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award (UL1RR029876) from the National Center for Advancing Translational Sciences, National Institutes of Health."

"The systemic impact of severe burn injury results in a variety of disorders that require therapeutic intervention. Propranolol, a nonselective β1, β2-adrenergic receptor antagonist, reduces resting heart rate and cardiac work caused by elevated circulating catecholamines. Oxandrolone, a testosterone mimetic, promotes protein synthesis and anabolism to counter muscle wasting. Coadministration of these drugs is expected to synergistically improve patient outcomes. Testosterone administration is known to alter β-adrenergic receptor-mediated signaling. Here, we determined whether the coadministration of oxandrolone alters plasma propranolol concentrations. Ninety-two pediatric patients with burns covering ≥30% of the TBSA were enrolled in this institutional review board-approved study and randomized to receive propranolol (n = 49) or oxandrolone + propranolol (n = 43). Plasma propranolol concentrations were determined following two dosing strategies: Q6 (liquid formulation; n = 86) and Q24 (extended-release capsule; n = 22). Samples were drawn before drug administration and at regular intervals throughout the next two dosing periods. Heart rate and blood pressure were recorded throughout the study. Propranolol half-life was 3.3 hours for the Q6 drug dosing frequency (P < .0001) and 11.2 hours for the Q24 strategy (P < .0001). Percentage of predicted heart rate declined by 2.8% for each doubling of the propranolol concentration in the Q6 dosing schedule (P < .0001). Percentage of predicted heart rate declined by 2.5% for each doubling of propranolol concentration on the Q24 dosing schedule (P < .0001). Maximum and minimum propranolol plasma concentrations were similar with either dosing regimen. The addition of oxandrolone did not affect any of the measured parameters. Oxandrolone coadministration does not alter propranolol’s plasma concentration, half-life, or effect on heart rate. This study is registered at clincialtrials.gov: NCT00675714."