caa a22 4500 465812279 CHVBK 20180323112120.0 cr unu---uuuuu 170327e19900701xx s 000 0 eng 10.1007/BF03190205 doi (NATIONALLICENCE)springer-10.1007/BF03190205 Evaluation of hepatic dysfunction in endotoxin pretreated rats using tolbutamide as a marker [Elektronische Daten] [Juzar Kaka, Khalil Al-Khamis, Musbah Tanira] Summary: The pharmacokinetics of tolbutamide (TB) have been studied in endotoxin pretreated rats with the aim of evaluating TB as a marker for endotoxin effects. Endotoxin dose of 10 mg/kg resulted in a 50% rate of mortality. TB was i.v. administered 24 h. after endotoxin dosing. Clearance (CI) decreased by approximately 2/3 of its value, area under the curve (AUC) and half-life (t1/2) in the pretreated animals were an average 1.5 times the values for the respective controls. Volume of distribution (Vd) increased by 10% approximately. These findings suggest that endotoxin pretreatment may cause hepatic damage by producing a decrease in Cl and an increase in the t1/2 of TB. But, SGOT levels in pretreated animals were no significantly different. This phenomenon may be explained by the increase in plasma protein binding of TB during endotoxin pretreatment, which decreases the free fraction of the drug in plasma available for metabolism. Endotoxin increased tmax of hydroxy-TB, while no change in Cmax was observed. Since tmax is inversely related to the formation and elimination rates of hydroxy-TB1 an increase in tmax may be due to the decrease in both elimination rates. No change in Cmax may be due to the decrease in the rate of formation which is equivalent to the decrease in the rate of elimination of hydroxy-TB. Springer-Verlag, 1990 Tolbutamide nationallicence endotoxin nationallicence hepatic dysfunction nationallicence rats nationallicence Kaka Juzar Department of Clinical Pharmacy, King Saud University, College of Pharmacy, P.O. Box 2457, 11451, Riyadh, Saudi Arabia aut Al-Khamis Khalil Department of Clinical Pharmacy, King Saud University, College of Pharmacy, P.O. Box 2457, 11451, Riyadh, Saudi Arabia aut Tanira Musbah Department of Clinical Pharmacy, King Saud University, College of Pharmacy, P.O. Box 2457, 11451, Riyadh, Saudi Arabia aut European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/3(1990-07-01), 203-209 0378-7966 15:3<203 1990 15 13318 https://doi.org/10.1007/BF03190205 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF03190205 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kaka Juzar Department of Clinical Pharmacy, King Saud University, College of Pharmacy, P.O. Box 2457, 11451, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Al-Khamis Khalil Department of Clinical Pharmacy, King Saud University, College of Pharmacy, P.O. Box 2457, 11451, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Tanira Musbah Department of Clinical Pharmacy, King Saud University, College of Pharmacy, P.O. Box 2457, 11451, Riyadh, Saudi Arabia aut NATIONALLICENCE 773 0- European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/3(1990-07-01), 203-209 0378-7966 15:3<203 1990 15 13318 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer