Investigation of the pharmacokinetics of celecoxib by liquid chromatography-mass spectrometry.
A new method for the quantification of celecoxib in human plasma based on reversed-phase high-performance liquid chromatography (HPLC) coupled to atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) after liquid-liquid extraction is presented. The method is rapid, sensitive and highly selective. The retention time of celecoxib was 2.3 min. The limit of quantification was 5 microg/L. Rofecoxib was used as internal standard. After validation, the method was used to study the pharmacokinetic profile of celecoxib following administration of a single oral dose (200 mg) in 12 healthy volunteers. Since celecoxib should be metabolized primarily by cytochrome 2C9 (CYP2C9), a poor metabolizer (PM) for this cytochrome P450 enzyme was included in the study. Pharmacokinetic characteristics (mean +/- SD) of extensive metabolizers (EM) were t(max) 2.9+/-1.2h, c(max) 842+/-280 microg/L, AUC(infinity) 6246+/-2147 microg h/L and t(1/2) 7.8+/-2.7h. The area under the curve (AUC(infinity)) for the PM was 12561 microg h/L. However, we found no noticeable increase in half life in the PM (11.5 h) after a single dose of celecoxib.
Werner
Ulrike
U
Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nuremberg, D-91051 Erlangen, Germany. ulrike.werner@pharmakologie.uni-erlangen.de
Werner
Dierk
D
Pahl
Andreas
A
Mundkowski
Ralf
R
Gillich
Martin
M
Brune
Kay
K
D000284:Administration, Oral; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D000068579:Celecoxib; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011110:Polymorphism, Genetic; D011720:Pyrazoles; D012015:Reference Standards; D012016:Reference Values; D012680:Sensitivity and Specificity; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D000068579:Celecoxib