G Sathyan1, K Sivakumar, J Thipphawong. 1. ALZA Corporation, 1900 Charleston Road, Mountain View, California 94039, USA. gsathyan@alzus.jnj.com
Abstract
OBJECTIVE: The purpose of this study was to investigate the pharmacokinetic properties of a novel, once-daily, controlled-release formulation of hydromorphone (OROS hydromorphone) in the presence of alcohol. RESEARCH DESIGN AND METHODS: In a single-centre, open-label, four-treatment, four-period, four-sequence, crossover study, two groups of 24 healthy subjects (fasted or fed) were randomised to receive four single doses of OROS hydromorphone 16 mg with solutions of either 0%, 4%, 20% or 40% alcohol, and with a naltrexone block. MAIN OUTCOME MEASURES: Plasma samples taken predose and at regular intervals up to 48 h after dosing were assayed for hydromorphone concentrations; a mixed-effect analysis of variance was done on log-transformed data. Bioequivalence was concluded if 90% confidence intervals of treatment mean ratios were between 80% and 125%. RESULTS:Plasma hydromorphone concentrations were slightly higher after dosing with all alcohol treatments in both the fasted and fed subject groups. Median T(max) values were between 12 and 16 h and ranges were similar for all treatments. C(max) values increased after alcohol compared with no alcohol, with the increase slightly lower in the fed state. The greatest mean increase in C(max) observed was 1.3-fold in the fasted state and 1.1-fold in the fed state. Confidence intervals were within 80-125% for AUC but were slightly higher for C(max). CONCLUSIONS: The pharmacokinetics of once-daily OROS hydromorphone were only minimally affected by alcohol, with no dose dumping of hydromorphone. The results indicate that the controlled-release properties of this formulation are maintained in the presence of alcohol.
RCT Entities:
OBJECTIVE: The purpose of this study was to investigate the pharmacokinetic properties of a novel, once-daily, controlled-release formulation of hydromorphone (OROS hydromorphone) in the presence of alcohol. RESEARCH DESIGN AND METHODS: In a single-centre, open-label, four-treatment, four-period, four-sequence, crossover study, two groups of 24 healthy subjects (fasted or fed) were randomised to receive four single doses of OROS hydromorphone 16 mg with solutions of either 0%, 4%, 20% or 40% alcohol, and with a naltrexone block. MAIN OUTCOME MEASURES: Plasma samples taken predose and at regular intervals up to 48 h after dosing were assayed for hydromorphone concentrations; a mixed-effect analysis of variance was done on log-transformed data. Bioequivalence was concluded if 90% confidence intervals of treatment mean ratios were between 80% and 125%. RESULTS: Plasma hydromorphone concentrations were slightly higher after dosing with all alcohol treatments in both the fasted and fed subject groups. Median T(max) values were between 12 and 16 h and ranges were similar for all treatments. C(max) values increased after alcohol compared with no alcohol, with the increase slightly lower in the fed state. The greatest mean increase in C(max) observed was 1.3-fold in the fasted state and 1.1-fold in the fed state. Confidence intervals were within 80-125% for AUC but were slightly higher for C(max). CONCLUSIONS: The pharmacokinetics of once-daily OROS hydromorphone were only minimally affected by alcohol, with no dose dumping of hydromorphone. The results indicate that the controlled-release properties of this formulation are maintained in the presence of alcohol.
Authors: Donna A Volpe; Ebenezer B Asafu-Adjaye; Christopher D Ellison; Suresh Doddapaneni; Ramana S Uppoor; Mansoor A Khan Journal: AAPS J Date: 2008-07-01 Impact factor: 4.009