title: Pharmacokinetic analysis of concentration data of drugs with irregular absorption profiles using multi-fraction absorption models.
abstract: Nonlinear regression analysis of plasma drug concentration data with irregular or stepwise absorption profiles was studied using multi-fraction absorption models in which drugs in the gastrointestinal tract were assumed to be divided into several fractions each with its respective lag time and absorption rate constant. Plasma allopurinol concentration data, with two-phase absorption profiles in dogs after oral administration, were found to be satisfactorily fitted using a two-fraction absorption model. Plasma sulfisoxazole concentration data in humans were also successfully analyzed using a two-fraction absorption model. Plasma and urinary concentrations of pindolol in humans after oral administration of sustained-release preparations were fitted to two- or three-fraction absorption models. The pharmacokinetic absorption behavior of a sustained-release preparation of diltiazem hydrochloride was studied using a multi-fraction absorption model. Pharmacokinetic parameters derived from these models and those from the discontinuous absorption model were compared.
mesh_terms: D000493:Allopurinol / Q000378:metabolism; D000818:Animals; D004110:Diltiazem / Q000378:metabolism; D004285:Dogs; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000097:blood / Q000378:metabolism*; D010869:Pindolol / Q000378:metabolism; D013444:Sulfisoxazole / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D000493:Allopurinol; D013444:Sulfisoxazole; D010869:Pindolol; D004110:Diltiazem