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Nabumetone and 6-MNA pharmacokinetics, assessment of intrasubject variability and gender effect

Publication at Faculty of Science, Faculty of Physical Education and Sport, First Faculty of Medicine |
2016

Abstract

In this study we describe pharmacokinetics (PK) of nabumetone, which has been previously studied mainly indirectly using its active metabolite. Since the 6-MNA pharmacokinetics suggests that nabumetone belongs to group of highly variable drugs (HVD), we have also evaluatedits intra- and inter- subject variability.We have developed and validated a rapid and sensitive HPLC-UV analytic method for analysis of both nabumetone and 6-MNA.

Results show that nabumetone reaches cmax with an average (+-SD) value of 0.5552 +- 0.2021 mg.l-1 at mean tmax of 8.63 +- 7.05 h, with mean AUClast of 18.069 +- 7.190 h.mg.l-1. There were no statistically significant differences between both sexes in PK of nabumetone, however for 6-MNA the mean +- SD AUClast was higher in men than in women with mean respective values of 721.2342 +- 185.5272 h.mg.l-1 and 545.2733 +- 97.6902 h.mg.l-1(p = 0.013), and clearance was lower in men 0.6536 +- 0.2177 l.h-1 in comparison with women 0.8760 +- 0.1751 l.h-1(p = 0.019).Inter-subject variability of nabumetone and 6-MNA was found to be between 35-45% and 10-30% for all assessed parameters (AUClast, cmax, partial AUCs), respectively.

The intra-subject variability was only modest, 15.59% and 6.40 % for AUClast for nabumetone and 6-MNA, respectively. The respective values of intra-subject variability for cmax were 13.66 % and 5.42 %.