Effect of probucol on the oral bioavailability of cyclosporine A

We have previously reported the reduction in oral bioavailability of cyclosporine A (CsA) by probucol, a lipid-lowering drug. To evaluate the mechanism, we examined the effect of probucol on the transport of CsA across Caco-2 cell monolayers, on the influence of CsA pharmacokinetics in rats, and on...

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Veröffentlicht in:	European journal of pharmaceutical sciences 2004-05, Vol.22 (1), p.71-77
Hauptverfasser:	Sugimoto, Koh-ichi, Sudoh, Toshiaki, Tsuruoka, Shuichi, Yamamoto, Yoshihisa, Maezono, Sachiko, Watanabe, Yoshiteru, Fujimura, Akio
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Animals Anticholesteremic Agents - administration & dosage Anticholesteremic Agents - pharmacology ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Bioavailability Biological and medical sciences Biological Availability Biological Transport, Active Caco-2 Caco-2 Cells Cyclosporine - antagonists & inhibitors Cyclosporine - pharmacokinetics Cyclosporine A General pharmacology Humans Intestinal Absorption - drug effects Male Medical sciences P-glycoprotein Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Probucol Probucol - administration & dosage Probucol - pharmacology Rats Rats, Wistar Spectrophotometry, Ultraviolet Time Factors
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Zusammenfassung:	We have previously reported the reduction in oral bioavailability of cyclosporine A (CsA) by probucol, a lipid-lowering drug. To evaluate the mechanism, we examined the effect of probucol on the transport of CsA across Caco-2 cell monolayers, on the influence of CsA pharmacokinetics in rats, and on the change of ultraviolet-absorption spectrum of the drug. Pretreatment with probucol (50 μM) inhibited ( P
ISSN:	0928-0987 1879-0720
DOI:	10.1016/j.ejps.2004.02.009