Hiroyuki Yasui

Analysis of arterial–venous blood concentration difference of drugs based on recirculatory theory with fast inverse laplace transform (FILT)

An arterial and venous blood (or plasma) concentration difference of drugs across the lung of rats was evaluated based on the recirculatory concept. The recirculatory system is given by the combination of the transfer functions for the pulmonary and the systemic circulations and is described by a Laplace-transformed equation, i.e., an image equation. For the manipulation of the image equations, the fast inverse Laplace transform (FILT) was adopted and MULTI(FILT) was used for the simultaneous curve fitting to estimate the pharmacokinetic parameters in the recirculatory model. Metoprolol as a test drug and cephalexin as a control drag were infused, respectively into the femoral vein for 30 min, and arterial and venous blood samples were collected simultaneously through the cannula at the femoral artery and at right atrium during and after the infusion. Exponential functions were assumed for the weight functions through both the pulmonary and systemic circulations. Results of the curve fitting showed that the single-pass extraction ratio through the pulmonary circulation (Ep)of meloprolol was about 0.2, whereas that of cephalexin was negligible. The mean transit times through the pulmonary circulation (¯tpof metoprolol and cephalexin were both about 0.5 min, which is small. The singlepass extraction ratios through the systemic circulation (Es)of metoprolol and cephalexin were both about 0.1. and the mean transit times through the systemic circulation (¯tswere 11.5 min and 8.2 min, respectively.

New hepatocellular diffusion model for analysis of hepatobiliary transport processes of drugs

AbstractA new hepatocellular diffusion model was developed to kinetically evaluate the hepatobiliary transport processes of drugs in the perfusion system, based on the physiological structure of the liver. Since the equations describing the hepatocellular diffusion phenomena were derived as image forms in the Laplace domain, the fast inverse Laplace transform (FILT) was adopted to manipulate the image equations. Cefixime and cefpiramide were selected as model drugs. The concentrations in the perfusate and the excreted amounts into the bile were simultaneously measured at appropriate intervals after the rapid administration of each drug into the portal vein. The hepatocellular diffusion model was fitted to the biliary excretion profiles from rat livers, by means of a nonlinear least squares program, MULTI(FILT). According to this model, the hepatobiliary transport process of drug is kinetically separated into three steps, that is, the diffusion into and through the hepatocytes, the transfer from the hepatocytes into the bile canaliculi, and the movement through the bile canaliculi to the outlet of bile duct. These steps are characterized by the diffusion rate constant through hepatocytes (kdif), the permeability rate constant into the bile canaliculi (kbmc) and the transit time through the bile canaliculi to the outlet of bile duct (

Moment analysis of hepatic local disposition of allopurinol and oxipurinol: metabolism kinetics from allopurinol to oxipurinol in the rat isolated perfused liver.

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Moment Analysis of Stereoselective Enterohepatic Circulation and Unidirectional Chiral Inversion of Ketoprofen Enantiomers in Rat

), respectively. It was demonstrated that kdif of cefixime (0.023min1) was significantly smaller than that of cefpiramide (0.044 min1), while the differences in kbmc and

Moment Analysis of Stereoselective Biliary Excretion and Chiral Inversion of Ketoprofen Enantiomers in Perfused Rat Liver

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Alternative continuous infusion method for analysis of enterohepatic circulation and biliary excretion of cefixime in the rat

were not obvious between cefixime and cefpiramide. kbmc and