Nabumetone and 6-MNA Pharmacokinetics, Assessment of Intrasubject Variability and Gender Effect

摘要

In this open-label, laboratory-blinded, 2-way single dose study in 24 volunteers of both sexes we found that (1) nabumetone reaches mean C-max +/- SD of 0.56 +/- 0.20 mgL(-1) at mean t(max) of 8.63 +/- 7.05 hours, and mean area under the curve (AUC)(last) of 18.07 +/- 7.19 hmgL(-1); (2) there are no statistically significant differences between both sexes in pharmacokinetics of nabumetone; (3) 6-methoxy-2-naphthylacetic acid (6-MNA) reaches higher AUC(last) in men compared with women (mean +/- SD, 721.23 +/- 185.53 hmgL(-1) and 545.27 +/- 97.69 hmgL(-1), respectively; P = 0.013); (4) there is lower 6-MNA clearance in men (0.65 +/- 0.22 Lh(-1)) in comparison with women (0.88 +/- 0.18 Lh(-1), P = 0.019), (5) intersubject variability of nabumetone and 6-MNA is between 35%-45% and 10%-30% for all assessed pharmacokinetics parameters (AUC(last), C-max, partial AUC values); (6) intrasubject variability (ISCV) for AUC(last) is low, 15.59% and 6.40% for nabumetone and 6-MNA, respectively, (7) ISCV for C-max is 13.66% and 5.42% for nabumetone and 6-MNA, respectively. Nabumetone thus belongs to compounds with low to moderate ISCV and therefore this product is expected to produce consistent effects in clinical practice.