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PIII‐59
Author(s) -
Schmith V. D.,
Fisher D.,
Foss J. F.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.267
Subject(s) - pharmacokinetics , medicine , metabolite , population , concomitant , pharmacology , oral administration , dosing , antibiotics , endocrinology , gastroenterology , chemistry , biochemistry , environmental health
AIM To characterize the population pharmacokinetics (PK) of alvimopan (ALV) & its metabolite (MET) in post‐operative ileus patients (POI) & healthy volunteers (HV) after oral dosing with ALV. METHODS Data from 9 HV studies (n=256) & 2 well‐controlled Phase III studies in POI (n=464) were combined to characterize the PK of ALV & MET using NONMEM. ALV PK was described by a two compartment model with oral absorption & a lag time. MET PK was described by a one‐compartment model with a catenary chain & lag time. Because MET is formed in stool by gut microflora, the input function for MET is the dose (and not plasma concentrations) of ALV. The effects of covariates on ALV & MET PK were evaluated. RESULTS & CONCLUSIONS The PK of ALV & MET were not related to weight, body mass index, gender, or renal function. Food resulted in a decrease in the rate & extent of absorption of ALV. Concentrations were 87% & 40% higher in POI than in HV for ALV & MET, respectively. ALV PK was related to age, but this effect was not clinically important because ALV concentrations were only ∼35% higher in a >70 yr old than in a <30 yr old. ALV PK was not affected by race. Compared to Caucasians, MET concentrations were 43% lower in black subjects & 82% lower in Hispanics following ALV administration. ALV PK was not affected by concomitant administration of acid blockers or antibiotics. MET concentrations were 49% lower in patients receiving acid blockers & 81% lower in subjects receiving preoperative antibiotics. Clinical Pharmacology & Therapeutics (2005) 79 , P74–P74; doi: 10.1016/j.clpt.2005.12.267