Fundamental understanding of drug absorption from a parenteral oil depot

• Published in: European journal of pharmaceutical sciences Vol. 83; pp. 19 - 27
• Main Authors: Kalicharan, Raween W., Schot, Peter, Vromans, Herman
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2016
• Subjects: Absorbance; Absorption, Physiological; Aged; Aged, 80 and over; Androgens - administration & dosage; Androgens - blood; Androgens - chemistry; Androgens - pharmacokinetics; Benzyl alcohol; Benzyl Alcohol - administration & dosage; Benzyl Alcohol - blood; Benzyl Alcohol - chemistry; Benzyl Alcohol - pharmacokinetics; Dosage Forms; Female; Humans; Injections, Intramuscular; Injections, Subcutaneous; Nandrolone; Nandrolone - administration & dosage; Nandrolone - analogs & derivatives; Nandrolone - blood; Nandrolone - chemistry; Nandrolone - pharmacokinetics; Oil depots; Pharmacokinetics; Sesame Oil - administration & dosage; Sesame Oil - chemistry; Sesame Oil - pharmacokinetics; Viscosity; Nandrolone decanoate (PubChem CID: 9677); Benzyl alcohol (PubChem CID: 244); Testosterone decanoate (PubChem CID: 155143); Oil depots; Haloperidol decanoate (PubChem CID: 52919); Benzyl alcohol; P; Absorbance; Nandrolone phenyl propionate (PubChem CID: 229455); ND; Nandrolone; BOH; Cholecalciferol (PubChem CID: 5280795); Pharmacokinetics
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2015.12.011

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. [Display omitted] •A study was initiated to determine in vivo nandrolone absorbance release out of an oil depot•Oil depot was administrated subcutaneously to elderly women•The pharmacokinetic profile of nandrolone is related to that of benzyl alcohol•Small molecules are directly absorbed, while larger, more lipophilic molecules exhibit an incomplete and slow absorption