Effects of dexamethasone to reverse decreased hepatic midazolam metabolism in rats with acute renal failure.

The inductive effects of dexamethasone on hepatic midazolam metabolism were examined in Wistar rats with acute renal failure (ARF) to clarify whether the ARF-related decrease in the hepatic expression of drug-metabolizing enzymes is caused by an impairment in the translation/polypeptide formation process.ARF was induced with intramuscular glycerol injection. Dexamethasone was orally administered.

Control of Nausea Based on Risk Analysis in Patients with Esophageal and Gastric Cancer Who Received Cisplatin-based Chemotherapy.

Background: Cisplatin is commonly used for esophageal and gastric cancer, but has a high emetic risk. Although the control of vomiting is favorable, nausea is still poorly controlled in patients receiving cisplatin-based regimens. The present study was designed to determine the risks for cisplatin-induced nausea.

Effect of carrageenan-induced acute peripheral inflammation on the pharmacokinetics and hepatic metabolism of midazolam in rats.

The effect of carrageenan-induced acute peripheral inflammation (API) on the pharmacokinetics of the hepatically metabolizing compound midazolam (MDZ) was investigated in rats. Rats were subcutaneously treated with λ-carrageenan in the hind paw to induce API. When MDZ was intravenously administered in male rats, it was demonstrated that the plasma concentration profile of MDZ slightly alters in API rats compared with that in normal rats, while the plasma concentrations of its metabolites, 4-hydroxy and 1'-hydroxy MDZ, are markedly reduced with delayed appearances in API rats.

Comparative study on altered hepatic metabolism of CYP3A substrates in rats with glycerol-induced acute renal failure.

To examine the mechanism accounting for the diverse alteration of hepatic metabolism of CYP3A substrates observed with renal function being severely impaired, the hepatic drug metabolizing activity was evaluated using liver microsomes prepared from rats with glycerol-induced acute renal failure (ARF). Midazolam, nifedipine and rifabutin were employed as representative CYP3A substrates. When the Michaelis-Menten parameters, K(m) and V(max) , were examined in the incubation study, the K(m) values of midazolam and nifedipine in ARF rats were shown to decrease by 50.