caa a22 4500 475819381 CHVBK 20180406123818.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1007/s002280000218 doi (NATIONALLICENCE)springer-10.1007/s002280000218 In-vivo indices of CYP2D6 activity: comparison of dextromethorphan metabolic ratios in 4-h urine and 3-h plasma [Elektronische Daten] [J. Chládek, G. Zimová, M. Beránek, J. Martínková] Abstract.: Objectives: Dextromethorpan (DM) is widely used as a probe drug to assess in vivo the activity of the cytochrome P450 2D6 (CYP2D6). The aim of the study was to compare metabolic ratios (MRs) of DM to dextrorphan (DEX) in plasma and urine. We examined, separately in urine and plasma, the relationships between the MRs which are based on DEX and those involving the sum of DEX and a secondary metabolite hydroxymorphinan (HM). Furthermore, we compared the MRs in plasma obtained with and without hydrolysis of DEX glucuronides. Methods: Concentrations of DM and metabolites in urine and plasma were determined by HPLC after a single oral dose of 30mg DM hydrobromide to 101 healthy Caucasian subjects. Urine was collected over the time interval 0-4h after the dose and plasma was obtained from 95 subjects 3h after administration. Results: Six subjects (5.9%) were of poor metaboliser (PM) phenotype (urinary DM:DEX ratio >0.3). A good correlation (r2=0.777, P<0.00001) was observed between the metabolic ratios of DM:DEX in plasma and urine. There was an excellent correlation, both in plasma and urine, between the log-transformed ratios of DM:DEX and of DM to the sum of molar concentrations of DEX and HM (r2>0.996, P<0.00001). Plasma samples of 89 subjects (83 EM and 6 PM) were analyzed without deconjugation of DEX glucuronide also. The correlation between the plasma ratios of DM:DEX based on unconjugated DEX and those involving glucuronide (r2=0.793, P<0.00001) was comparable to that reported by other authors on urine. Conclusion: In healthy Caucasian subjects, the MRs of DM to DEX in plasma obtained at 3h correlated reasonably well with those in urine collected over the time interval 0-4h after the dose. Nevertheless, repeatability of this plasma index should be determined before its wide use can be recommended. Finally, the interindividual variation in DEX metabolism to HM (catalyzed by CYP3A) contributes only minimally to the interindividual variability of the MRs. Springer-Verlag, 2000 Chládek J. Department of Pharmacology, Faculty of Medicine, Charles University Šimkova 870, 50001 Hradec Králové, Czech Republic aut Zimová G. Department of Pharmacology, Faculty of Medicine, Charles University Šimkova 870, 50001 Hradec Králové, Czech Republic aut Beránek M. Department of Clinical Biochemistry and Diagnostics, Faculty Hospital, Charles University, 50002 Hradec Králové, Czech Republic aut Martínková J. Department of Pharmacology, Faculty of Medicine, Charles University Šimkova 870, 50001 Hradec Králové, Czech Republic aut European Journal of Clinical Pharmacology Springer-Verlag 56/9-10(2000-12-01), 651-657 0031-6970 56:9-10<651 2000 56 228 https://doi.org/10.1007/s002280000218 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000218 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chládek J. Department of Pharmacology, Faculty of Medicine, Charles University Šimkova 870, 50001 Hradec Králové, Czech Republic aut NATIONALLICENCE 700 1- Zimová G. Department of Pharmacology, Faculty of Medicine, Charles University Šimkova 870, 50001 Hradec Králové, Czech Republic aut NATIONALLICENCE 700 1- Beránek M. Department of Clinical Biochemistry and Diagnostics, Faculty Hospital, Charles University, 50002 Hradec Králové, Czech Republic aut NATIONALLICENCE 700 1- Martínková J. Department of Pharmacology, Faculty of Medicine, Charles University Šimkova 870, 50001 Hradec Králové, Czech Republic aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 56/9-10(2000-12-01), 651-657 0031-6970 56:9-10<651 2000 56 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer