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 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; (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 and 545.27 ± 97.69 h·mg·L, respectively; P = 0.013); (4) there is lower 6-MNA clearance in men (0.65 ± 0.22 L·h) in comparison with women (0.88 ± 0.18 L·h, 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.
1Institute of Pharmacology, First Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic; and 2Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Prague 2, Czech Republic.
Svatopluk
S
Světlík
Martin
M
Štícha
Olga
O
Matoušková
Lenka
L
Nespěšná
Zbyněk
Z
Sklenář
Aleš
A
Bartůněk
František
F
Perlík
Ondřej
O
Slanař
D000328:Adult; D019540:Area Under Curve; D002074:Butanones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D000077430:Nabumetone; D009280:Naphthaleneacetic Acids / Q000493:pharmacokinetics*; D012737:Sex Factors; D055815:Young Adult
D002074:Butanones; D052246:Cyclooxygenase 2 Inhibitors; D009280:Naphthaleneacetic Acids; C044612:6-methoxy-2-naphthylacetic acid; D000077430:Nabumetone