sulindac and Liver-Diseases--Alcoholic

The pharmacokinetics of ibuprofen (Motrin) are best described by a two-compartment open model. Ibuprofen pharmacokinetics are only minimally influenced by advanced age, the presence of alcoholic liver disease, or rheumatoid arthritis. Levels of ibuprofen in breast milk are negligible. In addition, ibuprofen can be combined with acetaminophen without altering the pharmacokinetic profile. However, although not yet clinically proved, the concomitant use of ibuprofen and aspirin appears to reduce ibuprofen plasma levels to less than half those observed with ibuprofen alone.

Topics: Acetaminophen; Adult; Age Factors; Aged; Arthritis, Rheumatoid; Aspirin; Biological Availability; Chromatography, Gas; Chromatography, High Pressure Liquid; Drug Interactions; Female; Humans; Ibuprofen; Intestinal Absorption; Kinetics; Liver Diseases, Alcoholic; Male; Milk, Human; Models, Chemical; Sulindac; Time Factors

Ibuprofen and sulindac kinetics after oral doses were compared in 15 patients with alcoholic liver disease and 29 normal subjects. The patients with alcoholic liver disease were divided into a group with fair hepatic function (FHF) and a group with poor hepatic function (PHF) based on elimination rates of indocyanine green. The effects of alcoholic liver disease on the ibuprofen kinetics were minimal. The absorption of the drug appeared to be delayed in some of the PHF patients, and slight differences were noted in the serum AUC and the elimination rate constant for ibuprofen. The absorption of sulindac was delayed in both PHF and FHF groups of patients, as was the appearance of the active metabolite, sulindac sulfide, and the inactive metabolite, sulindac sulfone. The plasma AUC for sulindac sulfide in patients with poor hepatic function was four times that in normal subjects. The kinetics of sulindac, a pro-drug that relies on the liver for conversion to an active metabolite, were markedly affected by alcoholic liver disease.

Topics: Administration, Oral; Adult; Humans; Ibuprofen; Indenes; Kinetics; Liver Diseases, Alcoholic; Liver Function Tests; Middle Aged; Sulindac