Clinical pharmacokinetic of celecoxib in healthy Thai volunteers.
BACKGROUND
Celecoxib, a nonsteroidal antiinflammatory drug exhibits its antiinflammatory effect by selective inhibition of cyclooxygenase-2 (COX-2) enzyme. Its efficacy has been accepted for the treatment of arthritic pain with superior gastrointestinal side effect profile compared with other conventional NSAIDs.


OBJECTIVE
To elucidate clinical pharmacokinetic of celecoxib following an oral dose administration.


METHODS
Eighteen healthy Thai male volunteers were enrolled in the present study. Their mean age was 20.94 +/- 1.21 years and their mean weight was 63 +/- 5.17 kg. They were orally administered 200 mg celecoxib after an over night fasting, serial blood samples were drawn before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours after dosing. Plasma celecoxib was analysed by reversed-phase HPLC.


RESULTS
Following a 200 mg celecoxib oral administration, the drug was absorbed into the systemic circulation and reach maximum concentration (Tmax) within 2.50 +/- 1.22 hrs by average with the mean peak concentration (Cmax) of 686.83 +/- 211.35 ng/ml. The extent of absorption (area under the curve, AUC) was approximately 5157.12 +/- 1499.46 and 5911.48 +/- 1363.51 ng hr/ml for AUC(0-->t) and AUC(0-->infinity) respectively. The apparent volume of distribution (Vd) was found to be 458.93 +/- 323.28 L/hr. Celecoxib was eliminated after biotransformation and the metabolites were excreted in both urine and feces. The elimination half-life (t(1/2)) of celecoxib appeared to be 8.79 +/- 5.49 hrs with the apparent clearance (CL) of 35.91 +/- 9.85 L. The elimination rate constant for celecoxib obtained from this present study was about 0.11 +/- 0.05 hr(-1).


CONCLUSIONS
Pharmacokinetic parameters following an oral dose of 200 mg celecoxib administration were characterized, including Cmax, Tmax, Vd, kel, CL, AUC. These parameters reflected absorption, distribution, biotransformation and excretion of celecoxib in healthy Thai volunteers.
Itthipanichpong
Chandhanee
C
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Chompootaweep
Sumana
S
Wittayalertpanya
Supeecha
S
Kemsri
Wandee
W
Thaworn
Nongnuch
N
Lilitkarntrakul
Pajaree
P
Parikamsil
Sithiporn
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012016:Reference Values; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013785:Thailand
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib