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

In this open-label, laboratory-blinded, 2-way single dose study in 24 volunteers of both sexes we found that (1) nabumetone reaches mean Cmax ± SD of 0.56 ± 0.20 mg·L−1 at mean tmax of 8.63 ± 7.05 hours, and mean area under the curve (AUC)last of 18.07 ± 7.19 h·mg·L−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 AUClast in men compared with women (mean ± SD, 721.23 ± 185.53 h·mg·L−1 and 545.27 ± 97.69 h·mg·L−1, respectively; P = 0.013); (4) there is lower 6-MNA clearance in men (0.65 ± 0.22 L·h−1) in comparison with women (0.88 ± 0.18 L·h−1, P = 0.019), (5) intersubject variability of nabumetone and 6-MNA is between 35%–45% and 10%–30% for all assessed pharmacokinetics parameters (AUClast, Cmax, partial AUC values); (6) intrasubject variability (ISCV) for AUClast is low, 15.59% and 6.40% for nabumetone and 6-MNA, respectively, (7) ISCV for Cmax 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.
Source: American Journal of Therapeutics - Category: Drugs & Pharmacology Tags: Original Articles Source Type: research