title: Consideration on moments of outflow profile in liver perfusion system with change in perfusate flow rate using oxacillin as model drug.
abstract: The effect of perfusate flow rate on hepatic structure and hepatic uptake kinetics was investigated using oxacillin as a model drug and bovine serum albumin (BSA) as a reference substance in the liver perfusion system from the standpoint of a dispersion model and moment characteristics. The estimated recovery ratio (FH) of oxacillin was about 40% which was independent of the change in perfusate flow rate. The mean transit time (tH) of oxacillin decreased with an increase in flow rate, while the relative variance (sigma 2/t2H) of oxacillin was independent of the flow rate. The tH of BSA decreased with an increase in the flow rate to the same extent as that of oxacillin, while sigma 2/t2H of BSA was independent of flow rate. When the dispersion model is adopted as a model system to analyze hepatic perfusion data following the pulse input, the moment characteristics (FH, tH and sigma 2/t2H) are given in complicated equations. It is demonstrated by the present investigation that these moment equations can be extensively simplified for a drug with a medium extraction ratio (FH > 50%), i.e., FH is independent of the distribution, both FH and tH are independent of the dispersion process in the hepatic blood space, and both tH and sigma 2/t2H are independent of the elimination. Thus, it is shown that FH and tH are exactly the indices of elimination and distribution, respectively, and sigma 2/t2H is the index of dispersion in the blood space plus nonequilibrium in the hepatic distribution.
authors.affiliation: Faculty of Pharmaceutical Science, Kyoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohata
authors.forename: K
authors.initials: K
authors.lastname: Yamaoka
authors.forename: H
authors.initials: H
authors.lastname: Yasui
authors.forename: T
authors.initials: T
authors.lastname: Nakagawa
mesh_terms: D000818:Animals; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009929:Organ Size; D010068:Oxacillin / Q000493:pharmacokinetics*; D010406:Penicillins / Q000493:pharmacokinetics*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D010406:Penicillins; D012710:Serum Albumin, Bovine; D010068:Oxacillin