title: 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.
authors.affiliation: Department of Clinical Pharmacy, Division of Laboratory & Pharmacy, University Medical Centre Utrecht, P/O Box 85500, 3508 GA Utrecht, The Netherlands; Department of Pharmaceutics, UIPS, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands. Electronic address: r.kalicharan@umcutrecht.nl.
authors.forename: Raween W
authors.initials: RW
authors.lastname: Kalicharan
authors.affiliation: OrgaNext Research BV, Jansbuitensingel 7, 6811 AA Arnhem, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Schot
authors.affiliation: Department of Clinical Pharmacy, Division of Laboratory & Pharmacy, University Medical Centre Utrecht, P/O Box 85500, 3508 GA Utrecht, The Netherlands; Department of Pharmaceutics, UIPS, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: Vromans
mesh_terms: D065567:Absorption, Physiological; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D019905:Benzyl Alcohol / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004304:Dosage Forms; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000077603:Nandrolone Decanoate; D012715:Sesame Oil / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D014783:Viscosity
chemical_list: D000728:Androgens; D004304:Dosage Forms; D009277:Nandrolone; D012715:Sesame Oil; D000077603:Nandrolone Decanoate; D019905:Benzyl Alcohol
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)