caa a22 4500 477127479 CHVBK 20180405111654.0 cr unu---uuuuu 170330e19970401xx s 000 0 eng 10.1023/A:1012163919636 doi (NATIONALLICENCE)springer-10.1023/A:1012163919636 The Effect of RPR 102341 on Theophylline Metabolism and Phenacetin O-Deethylase Activity in Human Liver Microsomes [Elektronische Daten] [Rebecca White, Heleen Heyn, Jeffrey Stevens] Purpose. RPR 102341 is structurally similar to the fluoroquinolone class of antibiotics. Because some fluoroquinolones have been shown to inhibit theophylline metabolism, concomitant administration may increase plasma levels of theophylline resulting in serious adverse effects. The purpose of this study was to determine if RPR 102341 affects theophylline metabolism in vitro and, thus, predict whether a clinically significant drug interaction is likely to occur. In addition, the effect of RPR 102341 on phenacetin O-deethylase activity was determined to address the enzymatic basis of a potential drug interaction. Methods. The in vitro theophylline metabolism assay was conducted according to a modification of a published procedure. The phenacetin O-deethylase assay was conducted according to a modification of a published procedure. Results. The rate of conversion of theophylline to 3-methylxanthine in human liver microsomes in the presence of 100 μM and 500 μM RPR 102341 was 93.6 and 106 percent of the control reactions, respectively. The formation of 1-methylxanthine was 97.6 and 100 percent of the control, and 1,3-dimethyluric acid formation was 88.9 and 95.2 percent of control at 100 μM and 500 μM RPR 102341, respectively. In agreement, RPR 102341 caused no inhibition of human liver CYP1A2—catalyzed phenacetin O-deethylase activity. Finally, no inhibition was observed when RPR 102341 was incubated with human liver microsomes and an NADPH regenerating system prior to the addition of theophylline. Conclusions. Based on these studies, RPR 102341 is not expected to cause significant drug interactions with theophylline. Plenum Publishing Corporation, 1997 drug metabolism nationallicence human liver nationallicence antibiotics nationallicence cytochrome P450 nationallicence theophylline nationallicence phenacetin nationallicence cytochrome P4501A2 nationallicence White Rebecca Department of Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Research and Development, 19426-0107, Collegeville, Pennsylvania aut Heyn Heleen Department of Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Research and Development, 19426-0107, Collegeville, Pennsylvania aut Stevens Jeffrey Department of Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Research and Development, 19426-0107, Collegeville, Pennsylvania aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 512-515 0724-8741 14:4<512 1997 14 11095 https://doi.org/10.1023/A:1012163919636 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012163919636 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- White Rebecca Department of Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Research and Development, 19426-0107, Collegeville, Pennsylvania aut NATIONALLICENCE 700 1- Heyn Heleen Department of Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Research and Development, 19426-0107, Collegeville, Pennsylvania aut NATIONALLICENCE 700 1- Stevens Jeffrey Department of Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Research and Development, 19426-0107, Collegeville, Pennsylvania aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 512-515 0724-8741 14:4<512 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer