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. MATERIAL AND METHOD: 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). CONCLUSION: 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.

Antispasmodic effects of curcuminoids on isolated guinea-pig ileum and rat uterus.

Curcuminoids, a yellow constituent isolated from Curcuma longa Linn. rhizomes was studied for its antispasmodic activity in isolated guinea-pig ileum and rat uterus. Curcuminoids at the concentration of 12 microg/ml significantly inhibited the ileum pre-contracted with acetylcholine (ACh) 5 x 10(-7) M and histamine 5 x 10(-7) M. (Force of contraction was 62.84 +/- 4.66% and 75.60 +/- 4.66% respectively) and the effects were prominently observed when the concentration of curcuminoids was increased to 36 microg/ml. (Force of contraction was 44.93 +/- 4.33% and 42.79 +/- 1.98%). In potassium depolarizing Tyrode solution, curcuminoids 4 microg/ml and 20 microg/ml reduced the contraction induced by calcium chloride (CaCl2) 1.8 mM. (The contraction was 63.31 +/- 1.80% and 36.87 +/- 3.25%). In rat uterus smooth muscle preparation, curcuminoids 8 microg/ml and 16 microg/ml significantly reduced force and frequency of contraction induced by oxytocin 1 x 10(-2) IU/ml. Curcuminoids 8 microg/ml produced 54.68 +/- 3.34 per cent force of contraction and 79.09 +/- 2.29 per cent frequency of contraction. Curcuminoids 16 microg/ml caused more relaxation of rat uterus smooth muscle. (Force of contraction was 43.38 +/- 3.56%, frequency of contraction was 49.96 +/- 5.20%). Curcuminoids 8 and 16 microg/ml significantly reduced force of contraction induced by KCl 50 mM. (Force of contraction was 54.10 +/- 4.92% and 36.60 +/- 2.99%). The results obtained from this study concluded that curcuminoids produced a smooth muscle, relaxation effect on isolated guinea-pig ileum and rat uterus by receptor-dependent and independent mechanism.

Effects of managerial intervention on drug utilization pattern at King Chulalongkorn Memorial Hospital.

The economic crisis in Thailand since 1997 has a major impact on all sections of the country including health care. There were several suggestions for reducing the drug expenditure budget including restriction of hospital formulary, generic prescribing and generic dispensing. At King Chulalongkorn Memorial hospital, the new hospital formulary was established and implemented in March 1998. The generic dispensing policy was also in place at the same time. This study aimed to evaluate the impact of the new implementation by comparing the prescription patterns in out patient departments (OPDs) of the hospital before and after the new hospital formulary implementation. The prescriptions from several OPDs were systematically stratified samplings 5 weeks before and 5 weeks after March 1st, 1998. The information from the prescriptions including drug category, drug name, amount of dispensed drug, drug cost, etc. was collected and analyzed. The total number of prescriptions and the average number of drug items/prescription before and after the implementation were similar (2,049 vs 2,052, and 2.52 +/- 0.048 vs 2.45 +/- 0.03 respectively). The total cost of the prescription, the cost/prescription and the cost/item seemed to be different (1,690,484 baht vs 1,282,343 baht, 844 +/- 54.04 vs 633 +/- 41.11 and 332.58 +/- 29.59 vs 255.29 +/- 19.98 respectively). After the implementation, physicians in the hospital increasingly prescribed drugs by generic name (37.1% vs 44.85%). Locally made drugs were also prescribed by physicians and received by patients more than before (9.56% vs 84.27% and 28.15% vs 60.72%, respectively). Anti-infective agents were studied in depth as they contribute to significant amount of drug expenditure. The total cost of prescribed anti-infective agents and the cost/prescription were increased after the implementation (223,529 vs 274,435 Baht and 585.38 +/- 102.84 vs 772.71 +/- 147.59). The increased cost mainly came from the cost of anti-HIV drugs. Our data indicate that the new hospital formulary may have played a part on the impact of drug expenditure reduction and may have changed the prescribing attitude of physicians in King Chulalongkorn Memorial Hospital.