The effects of norepinephrine and prostaglandin E1 on pharmacokinetics of lidocaine in isolated perfused rat liver.
We hypothesized that depression of liver function by norepinephrine can be improved by prostaglandin E1. Isolated perfused rat liver was selected as an experimental model, since the flow rate can be regulated in it. Twenty-one rats were randomly allocated to three groups: control, norepinephrine, and norepinephrine and prostaglandin E1 groups. The liver was perfused in a recirculating system at a constant flow rate of 20 ml/min. After administration of two milligrams of lidocaine in each group, lidocaine and monoethylglycinexylidide concentrations in the recirculating system were measured. Lidocaine pharmacokinetics were analyzed using the SAAM II program, including metabolic rate from lidocaine to monoethylglycinexylidide using time-concentration curves. Norepinephrine significantly increased perfusion pressure and the area under the time-concentration curve for lidocaine. Norepinephrine decreased the clearance and the elimination rate constant of lidocaine compared with those in the control group. Although administration of prostaglandin E1 after infusion of norepinephrine did not significantly change perfusion pressure, it significantly (p < 0.05) improved metabolic rate, clearance and the elimination rate constant of lidocaine in the isolated rat liver model.
Matsuura
Y
Y
Department of Anesthesiology and Intensive Care Medicine, Osaka City University Medical School, Osaka, Japan.
Nishi
S
S
Kariya
N
N
Shimadzu
K
K
Asada
A
A
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D017082:Portal Pressure / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D008012:Lidocaine; C001173:monoethylglycinexylidide; D000527:Alprostadil; D009638:Norepinephrine