BIOMAT Database Logo BIOMAT Database Logo

Bioconversion of naltrexone and its 3-O-alkyl-ester prodrugs in a human skin equivalent. 2005

Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082, USA.

The purpose of this study was to compare the percutaneous absorption and bioconversion of naltrexone (NTX), naltrexone-3-O-valerate (VAL), and naltrexone-3-O-(2'-ethylbutyrate) (ETBUT) in a human skin equivalent model (EpiDerm) and in fresh human skin in vitro. NTX diffusion and metabolism to 6-beta-naltrexol (NTXol) were quantitated and compared in the EpiDerm and in excised fresh human skin. VAL and ETBUT diffusion and bioconversion studies were also completed in EpiDerm. Naltrexone bioconverted to levels of 3+/-2% NTXol in the EpiDerm and 1+/-0.5% in fresh human skin. VAL hydrolyzed rapidly in the EpiDerm and mainly (93+/-4%) NTX was found in the receiver compartment, similar to human skin. More intact ETBUT permeated the EpiDerm tissue compared to VAL, and only 15+/-11% NTX was found in the receiver. Significantly higher fluxes of NTX and the prodrugs were observed with the EpiDerm compared to human skin. A similar flux enhancement level was observed for VAL, compared to NTX base, in the EpiDerm and the human skin. Metabolically active human epidermal models like EpiDerm are useful as an alternative experimental system to human skin for prediction of topical/transdermal drug/prodrug bioconversion.

UI MeSH Term Description Entries
D009271 Naltrexone Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D009292 Narcotic Antagonists Agents inhibiting the effect of narcotics on the central nervous system. Competitive Opioid Antagonist,Narcotic Antagonist,Opioid Antagonist,Opioid Antagonists,Opioid Receptor Antagonist,Opioid Reversal Agent,Competitive Opioid Antagonists,Opioid Receptor Antagonists,Opioid Reversal Agents,Agent, Opioid Reversal,Agents, Opioid Reversal,Antagonist, Competitive Opioid,Antagonist, Narcotic,Antagonist, Opioid,Antagonist, Opioid Receptor,Antagonists, Competitive Opioid,Antagonists, Narcotic,Antagonists, Opioid,Antagonists, Opioid Receptor,Opioid Antagonist, Competitive,Opioid Antagonists, Competitive,Receptor Antagonist, Opioid,Receptor Antagonists, Opioid,Reversal Agent, Opioid,Reversal Agents, Opioid
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D002087 Butyrates Derivatives of BUTYRIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxypropane structure. Butyrate,n-Butyrate,Butanoic Acids,Butyric Acids,Acids, Butanoic,Acids, Butyric,n Butyrate
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004058 Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT. Diffusions
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.

Related Publications

Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Human skin permeation of 3-O-alkyl carbamate prodrugs of naltrexone.
August 2009, Journal of pharmaceutical sciences,
Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Human skin permeation of branched-chain 3-0-alkyl ester and carbonate prodrugs of naltrexone.
May 2005, Pharmaceutical research,
Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Permeation of buprenorphine and its 3-alkyl-ester prodrugs through human skin.
October 1996, Pharmaceutical research,
Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
In vivo evaluation of 3-O-alkyl ester transdermal prodrugs of naltrexone in hairless guinea pigs.
February 2005, Journal of controlled release : official journal of the Controlled Release Society,
Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Physicochemical evaluation, in vitro human skin diffusion, and concurrent biotransformation of 3-O-alkyl carbonate prodrugs of naltrexone.
July 2004, Pharmaceutical research,
Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Straight-chain naltrexone ester prodrugs: diffusion and concurrent esterase biotransformation in human skin.
December 2002, Journal of pharmaceutical sciences,
Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Enzymes involved in the bioconversion of ester-based prodrugs.
June 2006, Journal of pharmaceutical sciences,
Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Skin permeation and ex vivo skin metabolism of O-acyl haloperidol ester prodrugs.
February 2009, International journal of pharmaceutics,
Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Binding of prednisolone and its ester prodrugs in the skin.
February 1997, Pharmaceutical research,
Dana C Hammell, and Elzbieta I Stolarczyk, and Mitch Klausner, and Mohamed O Hamad, and Peter A Crooks, and Audra L Stinchcomb
Carbamate ester prodrugs of dopaminergic compounds: synthesis, stability, and bioconversion.
August 1991, Journal of pharmaceutical sciences,
Copied contents to your clipboard!