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Effect of food on kinetics of the nonsteroidal anti‐inflammative, alclofenac
Author(s) -
Sennello Lawrence T.,
Sonders Robert C.,
Friedman Nadav
Publication year - 1978
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 - 10.1002/cpt1978234414
Subject(s) - pharmacokinetics , absorption (acoustics) , half life , crossover study , oral administration , chemistry , pharmacology , drug , lag time , meal , urine , dosing , bioavailability , medicine , biochemistry , food science , biology , placebo , physics , alternative medicine , pathology , acoustics , biological system
Two clinical studies were conducted on the kinetics of alclofenac in healthy adult male volunteers. The first involved 32 subjects, each of whom received a single oral 500‐mg dose of alclofenac as an aqueous suspension to study the oral pharmacokinetics of the drug. The second involved 19 subjects in a three‐way crossover design to compare the effect of food eaten shortly before or shortly after dosing with that under fasting conditions. Alclofenac taken as an aqueous suspension under fasting conditions had a mean absorption half‐life of 15 min and a mean elimination half‐life of 1.5 to 2.0 hr. The calculated time of maximum plasma drug concentration was about 0.8 hr, with no appreciable absorption lag time. The pharmacokinetics were better described by the one‐compartment open model with first order absorption than by the two‐compartment one. Alclofenac taken shortly before or after a meal displayed a pharmacokinetic pattern that was poorly described by a model with first‐order absorption. A model with zero‐order absorption and first‐order elimination was a better fit. Elimination half‐life was much the same as the fasting state. Although calculated peak plasma drug levels were significantly delayed and decreased by food, the total amount of drug absorbed (based upon areas under curves) was not affected. About 10% to 15% of an orally administered dose was found in the 0 to 24 hr urine as parent drug in both conditions.