Pharmacokinetics and the most suitable regimen of panipenem/beta mipron in critically ill patients receiving continuous renal replacement therapy: a pilot study.

Critically ill patients often have complications of acute renal failure induced by severe infection or sepsis. The patients need administration of broad-spectrum antibiotics as well as continuous renal replacement therapy (CRRT). However, there is no uniform pharmacokinetics of antibiotics during the CRRT because CRRT is performed with the various combinations of dialysate flows (QD) and ultrafiltrate flows (QF).

Inhibitory effects of nicardipine to cytochrome P450 (CYP) in human liver microsomes.

To anticipate drug-drug interactions by nicardipine in vivo, cytochrome P450 (CYP) forms responsible for the metabolism of nicardipine and inhibition of CYP-dependent drug metabolism by nicardipine were investigated. Microsomes of human B-lymphoblastoid cells expressing each human CYP form were used for the metabolism of nicardipine. Inhibitory effects of nicardipine on drug metabolism were studied using human liver microsomes.

In vivo mutagenicities of damaged nucleotides produced by nitric oxide and ionizing radiation.

To evaluate the in vivo mutagenicities of damaged DNA precursors (deoxyribonucleoside 5'-triphosphates) produced by exposure to nitric oxide (NO) and ionizing radiation, five damaged deoxyribonucleotides (deoxyxanthosine triphosphate, deoxyoxanosine triphosphate, dITP, dUTP, and 8-hydroxy-dATP) were introduced into competent Escherichia coli cells. Their mutagenic potentials were assayed using the chromosomal rpoB gene as a mutagenesis target. In contrast to 8-hydroxy-dGTP and 2-hydroxy-dATP, which were examined in an earlier study, none of these damaged deoxyribonucleotides significantly increased the rpoB mutant frequency.

Co-operative regulation of the transcription of human dihydrodiol dehydrogenase (DD)4/aldo-keto reductase (AKR)1C4 gene by hepatocyte nuclear factor (HNF)-4alpha/gamma and HNF-1alpha.

Human dihydrodiol dehydrogenase (DD) 4/aldo-keto reductase (AKR) 1C4 is a major isoform of hepatic DD that oxidizes trans-dihydrodiols of polycyclic aromatic hydrocarbons to reactive and redox-active o-quinones and that reduces several ketone-containing drugs. To investigate the mechanism of transcriptional regulation of the human DD4 gene, the 5'-flanking region of the gene was fused to the luciferase gene. The results of luciferase assays using HepG2 cells and of 1,10-phenanthroline-copper footprinting indicated that two positive regulatory regions were located in regions from -701 to -684 and from -682 to -666.