Celebrex scientific update |
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PDA J Pharm Sci Technol. 2007 Mar-Apr;61(2):88-96.
Ali J, Tyagi P, Ahuja A, Baboota S, Hasan S.
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India.
Development and evaluation of a gastroretentive drug delivery system for the low-absorption-window drug celecoxib.
The objective of the present study is to develop microspheres for celecoxib to enhance its bioavailability by increasing its gastric residence time. Four different polymers-polyethylene oxide, Eudragit S, cellulose acetate, and Eudragit RL-were used to form the floating microspheres using an emulsion-solvent diffusion technique. The use of two different solvents (dichloromethane and ethanol) that differed in the rate of diffusion led to formation of a hollow core in the microspheres, which was partially responsible for the floatation ability. The formulation was optimized on the basis of in vitro buoyancy and in vitro release in simulated gastric fluid at pH 3. Scanning electron microscopy revealed differences between the formulations in terms of their topography. X-ray diffractometry and differential scanning calorimetery examination showed the amorphous nature of the drug. Microspheres prepared with polyethylene oxide:Eudragit S:celecoxib (2:2:1) gave the best in vitro percentage release and was taken as the optimized formulation. By fitting the data into zero order, first order, and Higuchi model, it could be concluded that the release followed first-order release kinetics. The correlation coefficient (R2 value) was obtained upon fitting the data to Higuchi equation, which signifies that the mechanism of release of celecoxib from the microspheres was diffusion rate-limited.
Can J Anaesth. 2007 May;54(5):342-8.
White PF, Sacan O, Tufanogullari B, Eng M, Nuangchamnong N, Ogunnaike B.
epartment of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9068, USA.
Effect of short-term postoperative celecoxib administration on patient outcome after outpatient laparoscopic surgery: [Effet de l'administration postoperatoire a court terme de celecoxib sur l'evolution des patients apres une chirurgie par laparoscop
PURPOSE: Non-opioid analgesics are increasingly used as part of a multimodal regimen for pain management. This prospective, randomized, double-blinded, placebo-controlled study was designed to evaluate the effect of short-term postoperative administration of celecoxib on pain management and recovery outcomes following laparoscopic surgery. METHODS: Eighty consenting ASA I-III outpatients undergoing laparoscopic surgery were randomly assigned to one of two treatment groups: Control (placebo) or Celecoxib (celecoxib, 400 mg.day(-1)). The initial dose (celecoxib 400 mg or placebo po) was administered in the recovery room, and celecoxib 200 mg (or a placebo) po bid was continued for three additional days after surgery. Postoperative pain scores and the need for opioid- containing analgesics were recorded at specific intervals in the recovery room. Follow-up evaluations were performed at 24 hr, 48 hr, 72 hr and seven days and one month after surgery to assess post-discharge pain, analgesic requirements, complications, quality of recovery, and resumption of normal activities, as well as patient satisfaction with their pain management. RESULTS: Celecoxib reduced mean pain scores and the need for analgesics at 24 hr and 48 hr postoperatively. Patient satisfaction with their postoperative pain management was also higher in the Celecoxib group (94 +/- 8 vs 80 +/- 25, P < 0.05). Quality of recovery scores were significantly higher in the Celecoxib group on the first and second postoperative days (17 +/- 1 vs 15 +/- 2, and 18 +/- 1 vs 16 +/- 2, respectively). Finally, bowel function recovered an average of one day earlier and patients resumed activities of daily living two days earlier in the Celecoxib group (P < 0.05). CONCLUSION: Short-term administration of celecoxib, 400 mg.day(-1) po, decreased postoperative pain and the need for opioid-containing analgesic medication, leading to an improved quality of recovery after outpatient laparoscopic surgery.
Mol Pharm. 2007 May 12;
Remenar JF, Peterson ML, Stephens PW, Zhang Z, Zimenkov Y, Hickey MB.
TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, Lexington, Massachusetts 02421, and Department of Physics & Astronomy, Stony Brook University, Stony Brook, New York
Celecoxib:Nicotinamide Dissociation: Using Excipients To Capture the Cocrystal's Potential.
The cocrystal of celecoxib and nicotinamide (Cel:Nic) was crystallized from chloroform in a 1:1 ratio, and the structure has been solved from powder X-ray diffraction data. The dissolution and solubility of Cel:Nic are medium dependent and can be attributed to differences in conversion of Cel:Nic to celecoxib polymorphs I and III (Cel-I and Cel-III). The presence of low concentrations of surfactants facilitates the rapid conversion of neat Cel:Nic to large aggregates of Cel-III that dissolve more slowly than commercial Cel-III into 1% SDS solution. In contrast, combinations of Cel:Nic with both 1-10% solid SDS and PVP wet rapidly and convert to a mixture of amorphous celecoxib and a micron-sized crystalline celecoxib form IV (Cel-IV), which has recently been shown to be up to 4-fold more bioavailable than marketed Cel-III. More than 90% of the suspended material dissolves within 2 min at 37 degrees C when transferred to 1% SDS solution. This example highlights the importance of exploring the form conversion of cocrystals in aqueous media prior to pharmacokinetic studies, and illustrates the potential of simple formulations to overcome the limitations caused by rapid dissociation of cocrystals and recrystallization of poorly soluble forms in aqueous media. Keywords: Polymorphs; pharmaceutical; cocrystal; nicotinamide; morphology; dissolution; stability; celecoxib; formulation.
Arch Dermatol Res. 2007 May 11;
Weberschock TB, Muller SM, Boehncke S, Boehncke WH.
Department of Dermatology, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature.
Adverse events triggered by non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drug-related intolerance reactions in medicine; they are possibly related to inhibition of cyclooxygenase-1. Coxibs, preferentially inhibiting cyclooxygenase-2, may therefore represent safe alternatives in patients with NSAID intolerance. We reviewed the literature in a systematic and structured manner to identify and evaluate studies on the tolerance of coxibs in patients with NSAID intolerance. We searched MEDLINE (1966-2006), the COCHRANE LIBRARY (4th Issue 2006) and EMBASE (1966-2006) up to December 9, 2006, and analysed all publications included using a predefined evaluation sheet. Symptoms and severity of adverse events to coxibs were analysed based on all articles comprising such information. Subsequently, the probability for adverse events triggered by coxibs was determined on analyses of double-blind prospective trials only. Among 3,304 patients with NSAID intolerance, 119 adverse events occurred under coxib medication. All adverse events, except two, have been allergic/urticarial in nature; none was lethal, but two were graded as life-threatening (grade 4). The two non-allergic adverse events were described as a grade 1 upper respiratory tract haemorrhage, and a grade 1 gastrointestinal symptom, respectively. In 13 double-blind prospective studies comprising a total of 591 patients with NSAID intolerance, only 13 adverse reactions to coxib provocations were observed. The triggering coxibs were rofecoxib (2/286), celecoxib (6/208), etoricoxib (4/56), and valdecoxib (1/41). This review documents the good tolerability of coxibs in patients with NSAID intolerance, for whom access to this class of drugs for short-term treatment of pain and inflammation is advantageous.
Ann Oncol. 2006 Sep 28;
Soo RA, Wu J, Aggarwal A, Tao Q, Hsieh W, Putti T, Tan KB, Soon WL, Lai YF, Mow B, Hsu S, Loh KS, Tan L, Tan P, Goh BC.
Department of Haematology-Oncology, National University Hospital, Singapore.
Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression.
BACKGROUND: Celecoxib is a selective cyclooxygenase-2 inhibitor with antitumor and antiangiogenic activity. We sought to determine pharmacodynamic change in tumors of patients with nasopharyngeal carcinoma (NPC) treated with celecoxib. METHODS: Tumor biopsies were obtained before and after treatment with celecoxib 400 mg b.i.d. for 14 days in patients with newly diagnosed, untreated NPC. Tumor angiogenesis and cell proliferation were assessed by immunohistochemistry and gene expression by microarray analysis. Plasma celecoxib concentrations were obtained on days 8 and 14. RESULTS: Paired samples were analyzed in 15 patients. Microvessel density was reduced in post-treatment samples and mean celecoxib levels reached therapeutic levels. Thirty-five genes (27 down-regulated, eight up-regulated) were differentially expressed on microarray analysis (p < 0.001). Down-regulated genes included cell cycle regulation-related (cyclin-dependent kinase 2, YES1), transcription factor (TRIP-Br2), whereas the antigen processing and presentation-related gene HLA-DM B was up-regulated. CONCLUSION: Celecoxib reduced angiogenesis and induced tumor transcriptional changes. Further characterization of these transcriptional changes in vivo is needed to provide further insights into the effects of celecoxib in neoplastic tissue. Our findings provide a rationale for clinical studies aimed at assessing the efficacy of celecoxib in the treatment of NPC.
Am J Orthop 2002 Aug;31(8):445-51
Ekman EF, Fiechtner JJ, Levy S, Fort JG
Southern Orthopaedic Sports Medicine, Providence Hospital Columbia, South Carolina, USA
Efficacy of celecoxib versus ibuprofen in the treatment of acute pain: a multicenter, double-blind, randomized controlled trial in acute ankle sprain
Ankle sprain is a common acute soft-tissue injury that often results in pain, inflammation, and ecchymosis. In this multicenter, double-blind, randomized parallel-group study, 445 adult patients received celecoxib 400 mg/day, ibuprofen 2,400 mg/day, or placebo for 10 days. Patients had experienced grade 1 or 2 ankle sprains within 48 hours and had moderate to severe ankle pain. Patient's Global Assessment of Ankle Injury responses, given on days 4 and 8, showed that the celecoxib group improved significantly more than the placebo group did, with 67% of the celecoxib group versus 55% of the placebo group improving at day 4 (P < .05). Patient's Assessment of Ankle Pain Visual Analog Scale on Weight Bearing responses, also given on days 4 and 8, showed that celecoxib was as efficacious in the treatment of ankle sprain as the maximum therapeutic dosage of ibuprofen and that, compared with placebo, it reduced pain significantly more (P < .05). The celecoxib group recovered and returned to function earlier (after 5 days) than did either the placebo group (8 days) or the ibuprofen group (6 days); the celecoxib-placebo difference was significant. Celecoxib, a cyclo-oxygenase-2-specific inhibitor with platelet-function-sparing properties, may be useful as a multimodal adjuvant in the treatment of ankle sprain.
Osteoarthritis Cartilage. 2005 Mar;13(3):206-10.
Detrembleur C, De Nayer J, van den Hecke A.
Rehabilitation and Physical Medicine Unit, Universite catholique de Louvain, Brussels, Belgium.
Celecoxib improves the efficiency of the locomotor mechanism in patients with knee osteoarthritis. A randomised, placebo, double-blind and cross-over trial.
OBJECTIVE: To compare the effect of celecoxib vs placebo treatment on clinical and gait variables in knee osteoarthritis (OA) patients; focusing on the efficiency of the locomotor mechanism. METHODS: Study design: A prospective, randomised, double-blind placebo-controlled trial. Patients: Eight adult patients with painful OA of the knee. Outcome measures: Clinical assessment included knee pain assessed by the visual analogue scale, range of knee motion assessed by goniometer, and locomotor function status assessed by a Knee Score Scale. Gait was assessed by means of instrumented analysis including synchronous kinematic, dynamic, electromyographic, and energetic recordings. Statistical analysis: The effect of treatment on the primary variable, the efficiency of the locomotor mechanism, and on secondary clinical and gait variables was assessed by the Hills and Armitage non-parametric approach. RESULTS: Celecoxib treatment improved the efficiency of the locomotor mechanism significantly. Among the secondary outcome measures assessed, celecoxib treatment improved walking cadence and reduced the knee pain significantly. CONCLUSION: This study shows that celecoxib is effective in improving locomotor function and pain in patients with knee OA.
Hepatology. 2005 Mar;41(3):579-87.
Claria J, Kent JD, Lopez-Parra M, Escolar G, Ruiz-Del-Arbol L, Gines P, Jimenez W, Vucelic B, Arroyo V.
DNA Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites.
Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti-inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX-2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis. This investigation consists of a double-blind, randomized, placebo-controlled trial aimed at comparing the effects of the selective COX-2 inhibitor celecoxib (200 mg every 12 hours for a total of 5 doses) on platelet and renal function and the renal response to furosemide (40 mg intravenously) with those of naproxen (500 mg every 12 hours for a total of 5 doses) and placebo in 28 patients with cirrhosis and ascites. A significant reduction (P < .05) in glomerular filtration rate (113 +/- 27 to 84 +/- 22 mL/min), renal plasma flow (592 +/- 158 to 429 +/- 106 mL/min) and urinary prostaglandin E(2) excretion (3430 +/- 430 to 2068 +/- 549 pg/min) and suppression of the diuretic (urine volume: 561 +/- 128 to 414 +/- 107 mL/h) and natriuretic (urine sodium: 53 +/- 13 to 34 +/- 10 mEq/h) responses to furosemide were observed in the group of patients treated with naproxen but not in the other two groups. Naproxen, but not celecoxib or placebo, significantly inhibited platelet aggregation (72% +/- 8% to 47% +/- 8%, P < .05) and thromboxane B(2) production (41 +/- 12 to 14 +/- 5 pg/mL, P < .05). In conclusion, our results indicate that short-term administration of celecoxib does not impair platelet and renal function and the response to diuretics in decompensated cirrhosis. Further studies are needed to evaluate the long-term safety of this drug in cirrhosis.
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Drug category:Antirheumatic
 Celebrex scientific update
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