title: Variability of bioavailability and intestinal absorption characteristics of bisoprolol.
abstract: We previously reported that renal function is partly responsible for the interindividual variability of the pharmacokinetics of bisoprolol. The aim of the present study was to examine the variability of bioavailability (F) of bisoprolol in routinely treated Japanese patients and intestinal absorption characteristics of the drug. We first analyzed the plasma concentration data of bisoprolol in 52 Japanese patients using a nonlinear mixed effects model. We also investigated the cellular uptake of bisoprolol using human intestinal epithelial LS180 cells. The oral clearance (CL/F) of bisoprolol in Japanese patients was positively correlated with the apparent volume of distribution (V/F), implying variable F. The uptake of bisoprolol in LS180 cells was temperature-dependent and saturable, and was significantly decreased in the presence of quinidine and diphenhydramine. In addition, the cellular uptake of bisoprolol dissolved in an acidic buffer was markedly less than that dissolved in a neutral buffer. These findings suggest that the rate/extent of the intestinal absorption of bisoprolol is another cause of the interindividual variability of the pharmacokinetics, and that the uptake of bisoprolol in intestinal epithelial cells is highly pH-dependent and also variable.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ishida
authors.forename: Asuka
authors.initials: A
authors.lastname: Horie
authors.forename: Maki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Masato
authors.initials: M
authors.lastname: Taguchi
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fujii
authors.forename: Takashi
authors.initials: T
authors.lastname: Nozawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001682:Biological Availability; D017298:Bisoprolol / Q000493:pharmacokinetics*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D002478:Cells, Cultured; D004155:Diphenhydramine / Q000494:pharmacology; D004347:Drug Interactions; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D011342:Procainamide / Q000493:pharmacokinetics; D011802:Quinidine / Q000494:pharmacology; D013696:Temperature
chemical_list: D004155:Diphenhydramine; D011802:Quinidine; D011342:Procainamide; D017298:Bisoprolol