Investigation of the pharmacokinetics of celecoxib by liquid chromatography–mass spectrometry

Abstract

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.

Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

“…Celecoxib. CYP2C9*3 has been associated with reduced celecoxib metabolism in vitro and in five of six in vivo studies (Kirchheiner et al, 2003e;Tang et al, 2001;Werner et al, 2002;Stempak et al, 2005;Lundblad et al, 2006). Individuals heterozygous and homozygous for CYP2C9*3 had 1.5-and 3.0-fold higher AUCs in one single-dose study (Kirchheiner et al, 2003e).…”

Celecoxib Up-Regulates the Expression of the ζ Chain of T Cell Receptor Complex in Tumor-Infiltrating Lymphocytes in Human Cervical Cancer

“…The duration and dosage of treatment were chosen on the basis of pharmacokinetic data (25). Treatment subjects received celecoxib from days 1 to 10 (400 mg b.i.d., at 8:00 a.m. and 8:00 p.m.).…”

Identification and Characterization of Novel Microsomal Prostaglandin E Synthase-1 Inhibitors for Analgesia

“…drugs effectively blocked PGE 2 production in LPS-stimulated human whole blood at their respective IC 80 concentrations (Huntjens et al, 2005). On this basis of observation, we initiated a biomarker-driven approach, which used IC 50 and IC 80 values from a human whole blood assay to determine compound efficacy (Werner et al, 2002). Our goal was to first identify molecules exhibiting high intrinsic potency in blocking PGE 2 production in LPS-stimulated human whole blood.…”

“…Our goal was to first identify molecules exhibiting high intrinsic potency in blocking PGE 2 production in LPS-stimulated human whole blood. Furthermore, a single oral dose of 200 mg celecoxib in humans provides blood levels of drug that, at C max , reach the in vitro human whole blood IC 80 value and exceed the IC 50 value for duration of 6-8 hours (Werner et al, 2002). Using these data, we sought compounds with high intrinsic potency that afforded exposure in rats approaching their IC 80 values in the human whole blood assay and remained above the human whole blood IC 50 for 6 hours or more after oral dosing (Schiffler et al, 2016).…”