celecoxib, Celebrex
Complexation of celecoxib with beta-cyclodextrin: Characterization of the interaction in solution and in solid state.

Sinha VR, Anitha R, Ghosh S, Nanda A, Kumria R.

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.

Inclusion complexation between celecoxib, a specific cyclooxygenase II inhibitor, and beta-cyclodextrin (beta-CD) was studied in solution and solid state. Drug cyclodextrin complexes were prepared by spray drying while physical mixtures were obtained by simple blending. Inclusion complexes were characterized by nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), infrared spectroscopy (IR), and polarimetry. Phase solubility analysis was carried out to determine the stability constant. Solubility studies revealed the existence of a 1:1 complex between celecoxib and beta-CD. NMR studies suggested a strong interaction between celecoxib and beta-CD prepared by spray drying. XRD and SEM analysis illustrated that celecoxib existed as an amorphous complexed form in spray-dried complexes. Dissolution studies showed that the celecoxib entrapped in spray-dried complexes dissolved much faster than the uncomplexed drug and physical mixtures. The data obtained suggest that celecoxib forms an inclusion complex with beta-CD in solution and solid state, which was confirmed by various analytical techniques. A shorter t(50%) of dissolution is found for the formulation prepared by spray drying when compared on a weight basis in a USP II apparatus. (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:676-687, 2005.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15668949&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Uptake of new drugs in rural and urban areas of Queensland, Australia: the example of COX-2 inhibitors.

Behan K, Cutts C, Tett SE.

School of Pharmacy, University of Queensland, Brisbane, QLD, 4072, Australia, s.tett pharmacy.uq.edu.au.

OBJECTIVE: This study compared the changes over time in the volume of prescriptions of COX-2 selective inhibitors between rural and urban Queensland to reveal any difference in the uptake of the prescribing of these new drugs between two geographically distinct areas. METHODS: This study used data from an administrative claims database. Dispensing data were obtained for celecoxib and rofecoxib in two areas, one rural and one urban, defined by postcodes. The numbers of consumers in these areas were similar and they were served by similar numbers of general practitioners. The number of defined daily doses (DDDs) of celecoxib and rofecoxib dispensed at specific times was calculated. RESULTS: Statistical analysis revealed no significant difference between the total numbers of DDDs of COX-2-selective non-steroidal anti-inflammatory drugs dispensed in the rural and urban groups over the period August 2000 to December 2002 (P=0.81). The rate of uptake of usage was also clearly similar between the urban and the rural groups. Total usage peaked in August 2000 in both groups (urban 39 DDD/1,000 people per day; rural 37 DDD/1,000 people per day), coinciding with the pharmaceutical benefits scheme (subsidized) listing of celecoxib. The number of DDDs declined dramatically in the following month, and then peaked again in May 2002 (urban 34, rural 36). The number of DDDs then steadily decreased in both areas after October 2002. CONCLUSION: The results suggest that the marketing of the new COX-2 inhibitors and the patients' anticipation of a safe and effective treatment have overcome the geographical boundaries of Queensland. Both areas had very high rates of uptake of the prescribing of these new drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15674626&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction.

Kimmel SE, Berlin JA, Reilly M, Jaskowiak J, Kishel L, Chittams J, Strom BL.

University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA.

BACKGROUND: Studies have postulated that cyclooxygenase-2 (COX-2) selective inhibitors affect cardiovascular risk through various mechanisms. Some of these mechanisms could increase risk (for example, inhibition of prostacyclin production), and some could decrease risk (for example, inhibition of inflammation). OBJECTIVE: To determine the effect of COX-2 inhibitors on risk for nonfatal myocardial infarction (MI). DESIGN: Case-control study. SETTING: 36 hospitals in a 5-county area. PARTICIPANTS: 1718 case-patients with a first, nonfatal MI admitted to these hospitals and 6800 controls randomly selected from the same counties. MEASUREMENTS: Self-reported medication use assessed through telephone interviews. RESULTS: The adjusted odds ratio for MI among celecoxib users, relative to persons who did not use nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), was 0.43 (95% CI, 0.23 to 0.79) compared with 1.16 (CI, 0.70 to 1.93) among rofecoxib users. The use of rofecoxib was associated with a statistically significant higher odds of MI compared with the use of celecoxib (adjusted odds ratio for rofecoxib vs. celecoxib, 2.72 [CI, 1.24 to 5.95]; P = 0.01). Nonselective NSAIDs were associated with a reduced odds of nonfatal MI relative to nonusers. Comparisons of COX-2 inhibitors with nonselective NSAIDs were the following: rofecoxib versus naproxen (odds ratio, 3.39 [CI, 1.37 to 8.40]) and celecoxib versus ibuprofen or diclofenac (odds ratio, 0.77 [CI, 0.40 to 1.48]). LIMITATIONS: The possibility of recall bias and uncontrolled confounding in this observational study limit the ability to make definitive conclusions. The association of celecoxib with a lower odds of MI could have occurred by chance. Only about 50% of eligible participants completed telephone interviews. CONCLUSION: Celecoxib and rofecoxib were associated with different odds of MI. Cardiovascular effects among the COX-2 inhibitors seem different, but further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors and potential differences among them.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15684203&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Celecoxib and radiation therapy in non-small-cell lung cancer.

Gore E.

Department of Radiation Oncology Medical College of Wisconsin Milwaukee, Wisconsin, USA.

Overexpression of cyclooxygenase-2 (COX-2) is frequently present in lung cancer and may play a significant role in carcinogenesis, invasion, and metastasis. It has been associated with shortened survival in patients with resected early-stage adenocarcinoma of the lung. COX-2 inhibition decreases tumor cell proliferation in vivo and has been shown to enhance tumor radiosensitivity. Additionally, COX-2 inhibition may protect normal pulmonary tissue from radiation fibrosis. Clinical studies are under way to assess the potential benefits and risks of COX-2 inhibition in the treatment of lung cancer. The rationale for COX-2 inhibitors in the treatment of lung cancer will be reviewed. The results of a phase II study assessing the acute toxicity of concurrent celecoxib (Celebrex) and thoracic irradiation in patients with non-small-cell lung cancer (NSCLC) are reported, and an ongoing Radiation Therapy Oncology Group study using celecoxib and concurrent radiation therapy for NSCLC in patients with intermediate prognostic factors is reviewed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15685827&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Cisplatin, fluorouracil, celecoxib, and RT in resectable esophageal cancer: preliminary results.

Govindan R, McLeod H, Mantravadi P, Fineberg N, Helft P, Kesler K, Hanna N, Stoner C, Ansari R, Fox E.

Alvin J. Siteman Cancer Center at Washington University School of Medicine St. Louis, Missouri 63110, USA. rgovinda im.wustl.edu

Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2) enzyme. In preclinical studies, COX-2 inhibition results in decreased cell proliferation and potentiation of chemotherapy and radiation. We report preliminary results of a phase II study conducted by the Hoosier Oncology Group in patients with potentially resectable esophageal cancer. All patients received cisplatin at 75 mg/m2 given on days 1 and 29 and fluorouracil (5-FU) at 1000 mg/m2 on days 1 to 4 and 29 to 32 with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) was administered at 200 mg orally twice daily beginning on day 1 until surgery and then at 400 mg orally twice daily until disease progression or unexpected toxicities, or for a maximum of 5 years. Esophagectomy was performed 4 to 6 weeks after completion of chemoradiation. The primary study endpoint was pathologic complete response (pCR). Secondary endpoints included response rate, toxicity, overall survival, and correlation between COX-2 expression and pCR. Thirty-one patients were enrolled from March 2001 to July 2002. Respective grade 3/4 toxicities were experienced by 58%/19% of patients, and consisted of granulocytopenia (16%), nausea/vomiting (16%), esophagitis (10%), dehydration (10%), stomatitis (6%), and diarrhea (31%). Seven patients (24%) required initiation of enteral feedings. There have been seven deaths so far, resulting from postoperative complications (2), pulmonary embolism (1), pneumonia (1), and progressive disease (3). Of the 22 patients (71%) who underwent surgery, 5 had pCR (22%). We conclude that the addition of celecoxib to chemoradiation is well tolerated. The pCR rate of 22% in this study is similar to that reported with the use of preoperative chemoradiation in other trials. Further follow-up is necessary to assess the impact of maintenance therapy with celecoxib on overall survival.

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celecoxib, Celebrex
Effect of Specific and Non-Specific Inhibition of COX-2 on Renal Oxygenation before and after Water Diuresis.

Gilbert S, Zuo C, Epstein FH.

Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass., USA.

Background/Aims: Water diuresis usually increases medullary oxygenation as a result of increased medullary synthesis of prostaglandins, but it is not clear whether this involves activation of cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2). Methods: The effects of celecoxib, a selective inhibitor of COX-2, and of ibuprofen, a non-specific inhibitor of COX-1 and COX-2, upon renal oxygenation during water diuresis were studied in a double-blind, prospective manner in 13 young women (age 24-34 years) using blood-oxygen level dependent magnetic resonance imaging. Celecoxib 200 mg b.i.d. for 4 days was compared with ibuprofen 80 mg b.i.d. for 4 days and with a placebo. Results: There was no effect of either drug on urinary volume, urinary osmolal concentration, or creatinine clearance. Water diuresis alone elicited a significant increase in oxygenation in borderline areas between cortex and medulla, which was eliminated by celecoxib or ibuprofen. Conclusion: Renal medullary oxygenation is improved by water diuresis in normal young women in a way that is blocked by a selective inhibitor of COX-2 as well as non-selective cyclooxygenase inhibitors. Selective COX-2 may be expected to have significant effects on renal functions. Copyright (c) 2005 S. Karger AG, Basel.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15692221&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Celecoxib and ketoprofen for pain management during tonsillectomy: a placebo-controlled clinical trial.

Nikanne E, Kokki H, Salo J, Linna TJ.

Department of Otorhinolaryngology, Central Hospital, Finland.

OBJECTIVE: To evaluate the efficacy and safety of celecoxib and ketoprofen in pain management during tonsillectomy in 120 patients. STUDY DESIGN AND SETTING: The study was randomized, double-blind, and placebo-controlled with parallel groups. Sixty minutes before anesthesia induction and 12 hours after, the patients received a 200-mg celecoxib, a 100-mg ketoprofen, or a placebo capsule. After discharge, patients were prescribed either celecoxib or ketoprofen capsules to be taken every 12 hours. RESULTS: During the first 24 hours, the need for rescue analgesic was less in the ketoprofen-group (5 [1-9]) doses (median [range]) than in the placebo-group (6 [1-13]) ( P = 0.021), but similar to the celecoxib-group (5 [2-14]). After discharge, the cessation of pain during eating occurred earlier in the celecoxib-treated patients, after 10 (1-17) days, than in the ketoprofen-treated patients, after 12 (1-21) days, ( P = 0.008). One celecoxib-treated patient and 6 ketoprofen-treated patients ( P = 0.013) needed electrocautery to stop postoperative bleeding. CONCLUSION: Ketoprofen provided a better initial analgesic efficacy but after discharge the recovery with celecoxib was faster and the incidence of secondary hemorrhages was lower. SIGNIFICANCE: Celecoxib seems to be more effective and safe than ketoprofen for pain management after discharge in patients with tonsillectomy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15692543&dopt=Abstract celecoxib, Celebrex