Limited role of P-glycoprotein in the intestinal absorption of cyclosporin A.
The contribution of P-glycoprotein (P-gp) to the intestinal absorption of cyclosporin A (CsA) was investigated by comparing the in vivo pharmacokinetics of CsA in P-gp knockout mice versus wild-type mice following both oral and intravenous administration and by examining the transport of CsA across Caco-2 cell monolayers. The apparent oral bioavailability of CsA in P-gp knockout mice was 1.55-fold larger than in wild-type mice, leading to an apparent absolute bioavailability of 41.8%. A concentration dependent efflux transport of CsA across Caco-2 cell monolayers was found, which exhibited saturation at a CsA concentration of 1 muM. These results suggest that the involvement of P-gp in the intestinal absorption of CsA is not as profound as was previously thought.
Lee
Young-Joo
YJ
Department of Pharmaceutics, College of Pharmacy, Seoul National University, Korea.
Chung
Suk-Jae
SJ
Shim
Chang-Koo
CK
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000818:Animals; D001682:Biological Availability; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D016572:Cyclosporine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016572:Cyclosporine