Fundamental understanding of drug absorption from a parenteral oil depot

Abstract

Oil depots are parenteral drug formulations meant for sustained release of lipophilic compounds. Until now, a comprehensive understanding of the mechanism of drug absorption from oil depots is lacking. The aim of this paper was to fill this gap. A clinical study with healthy volunteers was conducted. An oil depot with nandrolone decanoate and benzyl alcohol was subcutaneously administered in the upper arm of female volunteers. Pharmacokinetic profiles of both substances were related to each other and to literature data. Benzyl alcohol absorbs much more rapidly than nandrolone. In detail, it appears that benzyl alcohol enters the central compartment directly, while nandrolone decanoate is recovered in serum after a lag time. This lag time is also seen in literature data, although not reported explicitly. The absorption of nandrolone is enhanced by the presence of benzyl alcohol. This is most likely an effect of altered oil viscosity and partition coefficient between the oil and aqueous phase. The absorption rate constant of compounds is found to be related to the logP of the solubilized prodrug. The absorption rate is however not only determined by the physico-chemical properties of the formulation but also by the tissue properties. Here, it is argued that lymphatic flow must be considered as a relevant parameter.

Keywords: Absorbance; Benzyl alcohol; Benzyl alcohol (PubChem CID: 244); Cholecalciferol (PubChem CID: 5280795); Haloperidol decanoate (PubChem CID: 52919); Nandrolone; Nandrolone decanoate (PubChem CID: 9677); Nandrolone phenyl propionate (PubChem CID: 229455); Oil depots; Pharmacokinetics; Testosterone decanoate (PubChem CID: 155143).