Variability of Bioavailability and Intestinal Absorption Characteristics of Bisoprolol

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 absorptio...

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Bibliographic Details
Published in:DRUG METABOLISM AND PHARMACOKINETICS 2013, Vol.28 (6), p.491-496
Main Authors: Ishida, Kazuya, Horie, Asuka, Nishimura, Maki, Taguchi, Masato, Fujii, Nozomu, Nozawa, Takashi, Inoue, Hiroshi, Hashimoto, Yukiya
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Asian Continental Ancestry Group
bioavailability
Biological Availability
bisoprolol
Bisoprolol - pharmacokinetics
Cardiovascular Diseases - drug therapy
Cardiovascular Diseases - physiopathology
Cells, Cultured
Diphenhydramine - pharmacology
Drug Interactions
Epithelial Cells - metabolism
Female
Humans
Hydrogen-Ion Concentration
Intestinal Absorption
LS180 cell
Male
Middle Aged
nonlinear mixed effects model (NONMEM)
Procainamide - pharmacokinetics
Quinidine - pharmacology
Temperature
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Summary: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.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.DMPK-13-RG-017