Stability of Oxandrolone in Medium-Chain Triglyceride Oil and Pharmacokinetics Following Buccal Administration of the Extemporaneous Formulation in Neonates and Adults.

OBJECTIVES Growth failure following surgical palliation of complex congenital heart defects (CHDs) is a prognosticator of poor outcomes. Many strategies for improving weight gain have been implemented in this population, with limited success. We recently described the potential of the anabolic steroid oxandrolone to improve weight gain following surgical repair of CHD when administered via a medium-chain triglyceride (MCT) oil suspension to the buccal mucosa. The current study evaluates the stability of oxandrolone in the MCT oil formulation, as well as the pharmacokinetics of oxandrolone when administered via buccal mucosa in both neonates and adults. METHODS Stability was assessed by long-term storage of the preparation 1) at ambient conditions and 2) under photodegradative conditions for 3 days. Neonatal pharmacokinetic parameters were determined in a cohort of neonates following surgical CHD repair, whereas adult pharmacokinetics parameters were collected as part of a prospective study to evaluate the relative bioavailability of the oxandrolone in MCT oil formulation. RESULTS We found that oxandrolone was stable in the MCT oil formulation for at least 1 month, although exposure to light hastened drug degradation. Both neonatal and adult oxandrolone pharmacokinetics were variable; however, oxandrolone in MCT oil was relatively well absorbed through the buccal mucosa (mean bioavailability = 62.5%). CONCLUSIONS These data suggest that the variability in oxandrolone exposures is inherent to the drug, and not the formulation or route of administration. Combined, these data support further study of this novel oxandrolone in MCT oil formulation and its impact on growth following complex surgical repair of CHD in neonates.