caa a22 4500 475818083 CHVBK 20180406123814.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s002280050708 doi (NATIONALLICENCE)springer-10.1007/s002280050708 Circadian variation of the urinary 6β-hydroxycortisol to cortisol ratio that would reflect hepatic CYP3A activity [Elektronische Daten] [M. Ohno, I. Yamaguchi, T. Ito, K. Saiki, I. Yamamoto, J. Azuma] Objectives: Chronopharmacokinetics of drugs metabolized by cytochrome P 450 3A (CYP3A) has been reported recently; however, little is studied on intra-individual circadian variation in CYP3A activity in human. The aim of this study was to assess the intra-individual diurnal variation and day-to-day variation of the urinary 6β-hydroxycortisol to cortisol ratio, a noninvasive index of human CYP3A activity. Methods: Urine samples from ten healthy Japanese men were collected over four time intervals (0900 hours to 1300 hours, 1300 hours to 1700 hours, 1700 hours to 2100 hours and 2100 hours to 0900 hours) on days 1, 5 and 14 to verify diurnal variation, and 24-h urine was collected to study day-to-day variation over 2 weeks. Urinary 6β-hydroxycortisol and cortisol were determined by means of high-performance liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry. Results: The ratio of urinary 6β-hydroxycortisol to cortisol exhibited noteworthy diurnal variation intra-individually; 2.8-fold on average. However, day-do-day intra-individual variation of the ratio was not observed over 2 weeks; the coefficient of variation was 11.9 ± 3.0%. Conclusion: The result indicates that imprudent use of random urine has a great risk of false evaluation in assessment of the 6β-hydroxycortisol to cortisol ratio and that the ratio in 24-h urine samples provides a more robust measure of the inter-individual difference of this metabolic ratio, which to a certain but not complete extent represents the CYP3A activity. Springer-Verlag Berlin Heidelberg, 2000 Key words 6β-Hydroxycortisol nationallicence Cortisol nationallicence Circadian rhythm nationallicence Ohno M. Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada Oka, Suita, Osaka 565-0871, Japan e-mail: azuma@phs.osaka-u.ac.jp Tel.: +81-6-68798258; Fax: +81-6-68798259, JP aut Yamaguchi I. Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada Oka, Suita, Osaka 565-0871, Japan e-mail: azuma@phs.osaka-u.ac.jp Tel.: +81-6-68798258; Fax: +81-6-68798259, JP aut Ito T. Osaka Pharmacology Research Clinic, Japan, JP aut Saiki K. Kobe Pharmaceutical University, Japan, JP aut Yamamoto I. Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada Oka, Suita, Osaka 565-0871, Japan e-mail: azuma@phs.osaka-u.ac.jp Tel.: +81-6-68798258; Fax: +81-6-68798259, JP aut Azuma J. Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada Oka, Suita, Osaka 565-0871, Japan e-mail: azuma@phs.osaka-u.ac.jp Tel.: +81-6-68798258; Fax: +81-6-68798259, JP aut https://doi.org/10.1007/s002280050708 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050708 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ohno M. Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada Oka, Suita, Osaka 565-0871, Japan e-mail: azuma@phs.osaka-u.ac.jp Tel.: +81-6-68798258; Fax: +81-6-68798259, JP aut NATIONALLICENCE 700 1- Yamaguchi I. Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada Oka, Suita, Osaka 565-0871, Japan e-mail: azuma@phs.osaka-u.ac.jp Tel.: +81-6-68798258; Fax: +81-6-68798259, JP aut NATIONALLICENCE 700 1- Ito T. Osaka Pharmacology Research Clinic, Japan, JP aut NATIONALLICENCE 700 1- Saiki K. Kobe Pharmaceutical University, Japan, JP aut NATIONALLICENCE 700 1- Yamamoto I. Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada Oka, Suita, Osaka 565-0871, Japan e-mail: azuma@phs.osaka-u.ac.jp Tel.: +81-6-68798258; Fax: +81-6-68798259, JP aut NATIONALLICENCE 700 1- Azuma J. Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada Oka, Suita, Osaka 565-0871, Japan e-mail: azuma@phs.osaka-u.ac.jp Tel.: +81-6-68798258; Fax: +81-6-68798259, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer