title: Estimation of Michaelis-Menten constant of efflux transporter considering asymmetric permeability.
abstract: It was previously reported that the apparent K(m) values of P-gp in apical to basal (A to B) and basal to apical (B to A) directions were different. The purpose of the present study was to derive a theoretical framework by which this asymmetric concentration-permeability profile can be explained using a single intrinsic K(m) value. A three compartment model was used to represent the apical, cytosol and basal compartments. The difference of passive permeability and the surface areas between the apical and basolateral membrane were explicitly taken into account. Applying the steady state approximation and considering the mass balance in the cytosol compartment, an open analytical solution was obtained. By using this equation, the asymmetric concentration-permeability profile was appropriately reproduced. In addition, the expression level dependency of apparent K(m) was also reproduced.
authors.affiliation: Global Research & Development, Sandwich Laboratories, Research Formulation, Pfizer Inc., CT13 9NJ, Sandwich, Kent, UK. Kiyohiko.Sugano@pfizer.com
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Sugano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shirasaka
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003198:Computer Simulation; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000378:metabolism*; D010539:Permeability
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D026901:Membrane Transport Proteins