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Figure 2. The degrees of cyclooxygenase COX ; -selectivity of various traditional non-steroidal anti-infammatory drugs tNSAIDs ; and coxibs open circles ; . The concentrations required to inhibit COX-1 and COX-2 by 50% IC50 ; have been measured using whole blood assays of COX-1 and COX-2 activity in vitro.18 The line indicates equivalent COX-1 and COX-2 inhibition. Drugs plotted below the line are more potent inhibitors of COX-2 than drugs plotted above the line. The distance to the line is a measure of selectivity. Lumiracoxib is the compound with the highest degree of selectivity for COX-2 as its distance to the line is the largest. Celeckxib and diclofenac have similar degrees of COX-2 selectivity, as their distances to the line are similar; however, diclofenac is active at lower concentrations and, thus, located more to the left. Updated from FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001; 345: 433-442.
Efforts to Improve Access to Emergency Contraception In 1999, France became the first country in the world to distribute its brand of EC -- NorLevo -- in pharmacies without prescription or parental consent. NorLevo is also distributed free-of-charge along with other methods of contraception at family planning centers Ollivier, 1999 ; . In January 2000, France's Deputy Education Minister, Segolene Royal, took the unprecedented step of granting its school nurses the right to dispense EC in both junior and high schools Daley, 2000; McNeil, 2000 ; . The initiative was accompanied by a nationwide sex education campaign that included information on emergency contraception. Provision of EC in schools received widespread support from students, health practitioners, and the union of school nurses McNeil, 2000; Ollivier, 1999 ; . However, in July 2000 the Council of State, France's highest administrative court, overruled this decision citing a 1967 law that says hormonal contraception may only be distributed under prescription by pharmacies. The ruling followed a strong show of opposition by the Catholic Church and was lauded by the National Confederation of Catholic Family Associations, which also expressed regret that the court did not take additional steps to reaffirm parental authority in such matters McNeil, 2000 ; . In October 2000, the French Parliament amended the law to once again allow school nurses to dispense emergency contraception Kolata, 2000 ; . Restrictions on the dispensing of emergency contraception are easing in other countries as well. Women in 42 other countries, including Albania, Belgium, Canada, Denmark, Finland, India, Israel. 1325 N. Western Ave. Los Angeles 90027 Offers an emergency shelter and a transitional living program for youth with HIV AIDS between 18 and 21 years old. Services include crisis intervention, mental health, case management, substance abuse services, health care, art program, vocational services, education, outreach and spiritual ministry, for example, celecoxib mechanism of action. Up our sample included 2, 004 men and 2, 776 women, of whom 394 8.2% ; subjects used COX-2 inhibitors either rofecoxib or celecoxib ; daily Table 1 ; . Users of COX-2 inhibitors were older, were more likely to self-report osteoarthritis or rheumatoid arthritis, and had a slightly higher BMI. Daily use of ASA was reported by 1, 109 subjects 23% ; in the population studied, and the frequency of its use was not different between COX-2 daily users and non-users. Low-dose acetaminophen daily use was also common; 126 2.6% ; subjects reported daily use, and they were more likely to also use COX-2 inhibitors daily. All analyses reported are adjusted for previously described confounders and predictors of BMD. Effect of COX-2 inhibitor use on BMD In men, daily COX-2 inhibitor use was associated with lower BMD at all hip sites and with a similar effect at the lumbar spine, although at the lumbar spine the 95% confidence interval CI ; crossed the null value Fig. 1 ; . For example, the adjusted effect of COX-2 inhibitor daily use on total hip BMD in men was -3.1% 95% CI: -6.0, -0.3 ; . In contrast, among postmenopausal women not using estrogen replacement therapy, COX-2 inhibitor daily use was associated with a higher BMD Fig. 2 ; . For example. Heeded, this debacle could have been prevented and thus neither Merck nor the FDA fulfilled its responsibilities to the public. It is noted that even though the drug was approved in 1999 the data which was submitted to the licensing authorities were not available in a peer-reviewed journal for one and a half years after approval had been granted. In that article the cardiovascular data reported were incomplete. In 2001 an FDA advisory committee met to discuss concerns about potential cardiovascular risks - and this author feels that at this time there were sufficient grounds for concern for the FDA to have demanded that a trial should be conducted to specifically assess the cardiovascular risk and benefit of these agents. Since that time the author accuses Merck of issuing a relentless series of publications and sponsoring countless continuing medical education symposiums in an attempt to debunk the concern about adverse cardiovascular effects. He also raises concerns about the continuing direct to customer advertising campaigns that were carried on throughout this period. He postulates that if the excess incidence of MI or stroke seen in the VIGOR and ATTRACT trials are extrapolated to the total 10 million population exposed then up to 160, 000 patients may have developed MI or stroke because of exposure to this drug. This author calls for a full Congressional review of the case in order to avert such a catastrophe again. In another Perspective article that has also been published in advance, the author reviews the history of the VIGOR study assessing rofecoxib ; , the CLASS study assessing celecoxib ; , and the TARGET study assessing lumiracoxib ; to elucidate the data available on coxibs and cardiovascular disease. In VIGOR it was shown that rofecoxib recipients were 5 times more likely to have an MI. In CLASS the full data showed that celecoxib did not differ from traditional NSAIDs in their effect on predefined gastrointestinal endpoints and a retrospective analysis of the data reveals some signs of increased cardiovascular risk. In TARGET a non-significant increase in cardiovascular events was seen in non-aspirin users 0.26 vs 0.18 events per 100 patient years ; . The author also highlights the fact that parecoxib was associated with a cluster of cardiovascular events in patients undergoing CABG and was rejected by the FDA. In this article the author concludes that in the absence of definitive guidance COX-2 selective NSAIDS remain a rational choice for patients at a low cardiovascular risk who have serious gastrointestinal events, especially while taking traditional NSAIDs. Otherwise it would seem prudent to avoid coxibs in patients who have cardiovascular disease or are at risk for it. This author also concludes that it is now essential to determine whether the cardiovascular risk is or is not a class effect. He states that the burden of proof should rest with those who claim that this is a problem for rofecoxib alone and does not extend to other coxibs - as we must remember that, "the absence of evidence is not the evidence of absence". Title Source Lancet Editorial: VioxxTM: an unequal partnership between safety and efficacy Lancet 2004; 364 Link to homepage - article available to subscribers only and cleocin. The apparent reluctance to use agents such as celecoxib as first-line treatment probably stems from the fact they have not had the long medical track record of their nsaid counterparts, he said. WORLD HEALTH ORGANIZATION ANALGESIC LADDER: STEP 1--NONOPIOID ANALGESICS--NSAIDS, PART 1 PATHOPHYSIOLOGY OF INFLAMMATORY PAIN--A BRIEF LOOK Step 1 of the WHO Analgesic Ladder includes both acetaminophen see Pain Relief Connection Vol 1 #11 ; and nonsteroidal anti-inflammatory drugs NSAIDs ; . Inflammation is a complex process fundamental to immune response and healing, and contributes to many acute and chronic pain conditions. Tissue injury results in the release of the enzyme cyclooxygenase-2 COX-2 ; . COX-2, in turn, "stimulates the production of prostaglandin E2, which promotes a region of localized hypersensitivity surrounding the injury." The Scientist ; Other types of prostaglandins, stimulated by COX-1, are involved in production of the protective muscosa of the stomach, and the capacity of platelets to clump by becoming sticky. It is unclear what role COX-1 may have in pain and or inflammation. Nonsteroidal anti-inflammatory drugs NSAIDs ; are thought to provide pain relief primarily by targeting COX-2 at sites of inflammation. Both efficacy and toxicity of most NSAIDs is dose dependent. There has been a dramatic increase in scientific knowledge about NSAIDs in the past 30 years, and especially in the past 10 years. New NSAID classifications and drug selection criteria have been proposed based on the relative ability of a drug to inhibit COX-1, COX-2, or both. Some NSAIDs are also antipyretics. Most classes of NSAIDs "nonselective NSAIDs" ; target both COX-1 and COX-2 to a greater or lesser degree. The newer selective COX-2 inhibitors celecoxib, rofecoxib, and valdecoxib ; will be the subject of the February "Clinical Focus." SPECTRUM OF NSAIDS There are a large number of NSAIDs Micromedex, in the Partners Handbook, lists 64 drugs ; in roughly a halfdozen subclasses. Several are available over the counter, while most are available only by prescription. All NSAIDs are available for oral administration. A few are available in liquid formulations, as chewable tablets, as topical preparations, or as rectal suppositories. One, ketorolac, is available for parenteral administration. Aspirin is found in combination with many over the counter and prescription analgesic products and cold remedies. Ibuprofen is found in certain cold remedies and in combination with the opioids hydrocodone and oxycodone. PRINCIPLES OF NSAID THERAPY 1. When studied over large populations, no specific NSAID has been found to be more efficacious as an analgesic than the others. Drug and dose should be individualized to patient characteristics, including patient-reported pain relief. If pain is not sufficiently relieved with escalating doses of an NSAID over 2 weeks, trials with other NSAIDs may be attempted. 2. Assessment should include a history of what has worked in the past and what side effects were experienced. 3. For persistent pain syndromes such as arthritis, dosing should be scheduled rather than PRN. 4. Over the counter NSAIDs or acetaminophen should be considered first line treatment for mild to moderate acute or persistent pain. Note that moderate WHO Step 2 ; pain may require addition of an opioid and clomid. Dose causes failure of spermiation in the rat. Toxicol. Appl. Pharmacol. 121, 15-21. Hill, R. N., Erdreich, L. S., Paynter, O. E., Roberts, P. A., Rosenthal, S. L., and Wilkinson, C. F. 1989 ; . Thyroid follicular cell carcinogenesis. Fundam. Figure 4. Celefoxib docked into the -cyclodextrin dimer ball and sticks indicate celecoxib and colchicine. Gabriel; value health 2003, mar-apr; 6 2 144-5 osteoarthritis drug celebrex celecoxib ; less likely to cause increased blood pressure than vioxx rofecoxib european league against rheumatism eular ; conference proceedings. Celecoxib pharmacokineticsIf you had been taking vioxx, or are still taking one of the other cox-2s still on the market— celecoxib celebrex ; or valdecoxib bextra ; — it’ s time to talk to your doctor to find out if it makes sense to stay with your current medication, or switch to an alternative and erythromycin. Results Plasma Profiles of Drug and Total Radioactivity. The plasma concentrations of radioactivity and celecoxib are shown in Fig. 3. Peak plasma concentrations of radioactivity 2.75 0.45 g Eq ml ; were achieved at 1.75 0.30 h after dosing. Plasma concentrations of radioactivity had substantially decreased by 4 h after dosing. In all except two subjects, radioactive concentrations were below the limit of detection of the assay by 72 h after dosing. The AUC0 value for radioactivity was 22.7 1.8 g Eq h ml. The terminal elimination half-life of radioactivity was 17.0 h. The mean maximum plasma concentration and AUC0 48h values for celecoxib were 1.53 g ml and 8.71 g h ml, respectively. The mean time to maximal plasma concentration was 1.42 h. The mean elimination half-life of celecoxib was 11.5 h. Representative radiochromatograms of plasma samples obtained after the oral administration of [14C]celecoxib are shown in Fig. 4. In addition to celecoxib, three metabolites of celecoxib were observed in plasma. Two of the three metabolites coeluted on HPLC with authentic standards of the hydroxyl metabolite M-3 ; and a carboxylic acid metabolite M-2; Fig. 2 ; . The third peak coeluted at the same retention time as a 1-O-glucuronide of the carboxylic acid metabolite M-1 ; that was identified in urine. At 0.5 h after dosing, mean plasma celecoxib concentrations represented about 85% of total plasma radioactivity, whereas at the later time points 312 h after dosing ; , plasma celecoxib concentrations were 50 to 65% of the total radioactivity. The percentages of plasma radioactivity associated with each of these metabolites are listed in Table 1. Excretion of Administered Radioactivity. A summary of the excretion of radioactivity for the individual subjects is given in Table 2. The mean S.E. of the radiolabeled dose recovered in the urine, saliva, feces, and fecal wipes was 84.8 4.9%. The majority of the radioactivity was detected in fecal samples 57.6 7.3% ; and urine samples 27.1 2.2% ; , with only negligible amounts detected in.
Despite some similar characteristics, these drugs are clinically quite different from each other in their adverse effect profiles table 2. Acetylsalicylic acid and nonsteroidal anti-inflammatory drug intolerance. J. Asthma 36, 657 663 Quiralte, J., Saenz de San Pedro, B., and Florido, J. J. 2002 ; Safety of selective cyclooxygenase-2 inhibitor rofecoxib in patients with NSAID-induced cutaneous reactions. Ann. Allergy Asthma Immunol. 89, 63 66 Elder, C. L., Dahners, L. E., and Weinhold, P. S. 2001 ; A cyclooxygenase-2 inhibitor impairs ligament healing in the rat. Am. J. Sports Med. 29, 801 805 Simon, A. M., Manigrasso, M. B., and O'Connor, J. P. 2002 ; Cyclo-oxygenase 2 function is essential for bone fracture healing. J. Bone Miner. Res. 17, 963976 Kitahara, M., Eitner, F., Ostendorf, T., Kunter, U., Janssen, U., Westenfeld, R., Matsui, K., Kerjaschki, D., and Floege, J. 2002 ; Selective cyclooxygenase-2 inhibition impairs glomerular capillary healing in experimental glomerulonephritis. J. Am. Soc. Nephrol. 13, 12611270 Long, J., Lewis, S., Kuklo, T., Zhu, Y., and Riew, K. D. 2002 ; The effect of cyclooxygenase-2 inhibitors on spinal fusion. J. Bone Joint Surg. Am. 84-A, 17631768 Brown, K. M., Saunders, M. M., Kirsch, T., Donahue, H. J., and Reid, J. S. 2004 ; Effect of COX-2-specific inhibition on fracture-healing in the rat femur. J. Bone Joint Surg. Am. 86, 116 123 Goodman, S., Ma, T., Trindade, M., Ikenoue, T., Matsuura, I., Wong, N., Fox, N., Genovese, M., Regula, D., and Smith, R. L. 2002 ; COX-2 selective NSAID decreases bone ingrowth in vivo. J. Orthop. Res. 20, 1164 1169 Einhorn, T. A. 1999 ; Point of view Comment on Spine 1999; 24 21 ; : 2188 2194 ; . Spine 24, 21932194 Laulederkind, S. J., Thompson-Jaeger, S., Goorha, S., Chen, Q., Fu, A., Rho, J. Y., Ballou, L. R., and Raghow, R. 2002 ; Both constitutive and inducible prostaglandin H synthase affect dermal wound healing in mice. Lab. Invest. 82, 919 927 Blomme, E. A., Chinn, K. S., Hardy, M. M., Casler, J. J., Kim, S. H., Opsahl, A. C., Hall, W. A., Trajkovic, D., Khan, K. N., and Tripp, C. S. 2003 ; Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice. Br. J. Dermatol. 148, 211223 Wilgus, T. A., Vodovotz, Y., Vittadini, E., Clubbs, E. A., and Oberyszyn, T. M. 2003 ; Reduction of scar formation in full-thickness wounds with topical celecoxib treatment. Wound Repair Regen. 11, 2534 Gilroy, D. W., Colville-Nash, P. R., Willis, D., Chivers, J., Paul-Clark, M. J., and Willoughby, D. A. 1999 ; Inducible cyclooxygenase may have anti-inflammatory properties. Nat. Med. 5, 698 701 Warner, T. D., Giuliano, F., Vojnovic, I., Bukasa, A., Mitchell, J. A., and Vane, J. R. 1999 ; Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc. Natl. Acad. Sci. USA 96, 75637568 Received for publication June 26, 2003. Accepted for publication January 21, 2004. AGARWAL NK, VELP ANDIAN T, KUMAR A, KOTWAL PP GUPTA , SK Department of Pharmacology, All India Institute of Medical sciences, Ansari Nagar, New-Delhi-110029. Objective: To monitor the adverse drug reactions of newer COX2 inhibitors with special reference to instant release and conventional formulations of nimesulide. Methods: Post-Marketing Surveillance: A group of arthritis patients on routine therapy of selective COX-2 inhibitors Nimesulide-IR & Regular, Rofecoxib, and Celecoxbi ; were enrolled from the Immunology Clinic at AIIMS. Complete information regarding the patient was obtained and the baseline status assessed. Any new symptoms, sign or discrepancy with drug administration, as reported by the patient, was recorded and compared. Pharmacokinetic study: Two groups of 6 healthy males, were administered Nimesulide IR and Regular ; . Blook samples were collected at various time intervals and quantitated for Nimesulide using HPLC. The pharmacokinetic parameters were calculated and compared. Results: The adverse effects of the drugs were in the following order Nimesulide Celecoxib Rofecoxib. Intensity of these adverse effects was dose and time dependent. Nimesulide shows highest gastric intolerance 11% ; and hepatotoxicity 3.3% ; . Celecoxib exhibited renal toxicity 1.5% ; while Rofecoxib caused hypertension 1.5% ; . The pharmacokinetic parameters were significantly greater in instant release formulation than conventional formulation. Conclusion: Correlation of adverse effect profile with pharmcokinetic parameters shows that due to fast release of nimesulide IR in the stomach there is a greater incidence of its GIT intolerance, than regular nimesulide formulation. 13. ROLE OF ACTIVE CONSTITUENTS OF GLYCYRRHIZA GLABRA ON PARA- AND TRANSCELLULAR ABSORPTION. Bucci C1, Holbrook A2, 3, 4, Bates S4, Michael C5 1 Department of Pharmacy, Sunnybrook & Women's College Health Sciences Centre, Toronto, Canada; 2 Division of Clinical Pharmacology and Therapeutics, McMaster University, Hamilton, Canada; 3Centre for Evaluation of Medicines, St Joseph's Healthcare, Hamilton, Canada; 4Department of Medicine, McMaster University, Hamilton, Canada Corresponding Author: claudia.bucci sw Funding Source: none Background: A 70-year-old woman developed bilateral leg pain and a skin rash on both legs two days after initiating celecoxib therapy for left hip pain. She had no history of autoimmune disease or drug allergy but reported a remote pulmonary embolism post-surgery. In hospital, laboratory tests showed a positive cryoglobulin and cold agglutinin, elevated IgM and elevated liver function tests consistent with cryoglobulinemia. An erythrocyte sedimentation rate ESR ; was zero. She was treated with steroids, intravenous immunoglobulin and plasmapheresis. Despite treatment, the rash progressed to extensive ischemic necrosis, resulting in bilateral above knee amputation. A skin biopsy was consistent with ischemic changes and small vessel deposition with no evidence of inflammation or vasculitis. The differential diagnosis included hypercoagulable states such as cryoglobulinemia, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, paroxysmal nocturnal hemoglobinuria, protein C deficiency and antiphospholipid antibody. The necrosis and lack of mucosal involvement was considered not consistent with toxic epidermal necrolysis. The cryoglobulin was immunoglobulin M IgM ; kappa monoclonal ; consistent with Type I cryoglobulinemia, usually linked to lymphoproliferative disorders i.e., multiple myeloma, Waldenstrm macroglobulinemia ; , however this was never diagnosed. Results: It is well documented in the literature that COX-2 inhibitors may cause a prothrombotic state by decreasing prostacyclin PGI2 ; production. To date, there are no reports of celecoxib-induced cryoglobulinemia. There is. 13. In a trial by MacGregor 2006 ; of estradiol gel for short-term prophylaxis of menstrual migraine, the benefit of a 22 percent reduction in number of headache days was offset by: a. A 40 percent increase in the relative risk of migraine during the 5 days after cessation of estradiol treatment. b. A 40 percent increase in the relative risk of tension-type headache during the 5 days after cessation of estradiol treatment. c. A 10 percent increase in the relative risk of ischemic stroke. d. A 10 percent increase in the relative risk of hemorrhagic stroke. 14. In the United States, the indirect costs of migraine, in terms of time lost from work and reduced productivity, are estimated to be: a. More than 10 times higher than the direct costs of migraine. b. More than 5 times higher than the direct costs. c. About the same as the direct costs of migraine. d. More than 5 times lower than the direct costs. e. More than 10 times lower than the direct costs. 15. The only nonsteroidal anti-inflammatory drug that has been shown to be efficacious for shortterm prophylaxis of menstrual migraine is: a. Celecoxib. b. Diclofenac. c. Ibuprofen. d. Naproxen. e. Rofecoxib. 16. In comparison with their headaches at other times of their cycle, women referred to headache clinics experience menstrual migraines that are: a. More frequent. b. More severe. c. More often associated with vomiting. d. All the above. e. None of the above and cleocin. Allan Nickel, M.D. Chaffer SC, Concepcion LA, Nickel AE, Massive Lithium Overdose with Sustained Release Preparation: Case Report and Evaluation of Factors Influencing Removal by Hemodialysis. J Soc Nephrol, 2005; 16: 843A Khurana A, Runge VM, Narayanan M, Green JF Jr, Nickel AE, Nephronic systemic fibrosis: a review of 6 cases temporarily related to gadodiamide injection omniscan ; , Invest Radio. 2007 Feb; 42 2 ; : 139-45. Jules B. Puschett, M.D. Effects of celecoxib on renal carbonic anhydrase: a randomized controlled trial. A.B. Alper, H. Tomlin, U. Sadhwani, A. Whelton, J.B. Puschett. J Ther 13: 229-235, 2006. A rat model of preeclampsia. M. Ianosi-Irimie, J.D. Nadig, M.W. Williams, C.A. Pridjian, J.M. Whitbred, H.V. Vu, D.C. Wrenn, G. Pridjian, J.B. Puschett. Clin Exp Hypertens 8: 605-617, 2005.
Sites participating in this study were as follows: Massachusetts General Hospital Boston, MA ; , Columbia Presbyterian Medical Center New York, NY ; , Southwest Clinical Research Center Albuquerque, NM ; , University of Pittsburgh School of Medicine Pittsburgh, PA ; , Center for Health Studies Cleveland, OH ; , and Center for Women's Health and Sports Medicine Philadelphia, PA ; . Received January 6, 2003. Accepted April 10, 2003. Address all correspondence and requests for reprints to: Steven Grinspoon, M.D., Massachusetts General Hospital, Neuroendocrine Unit, Bul 457b, 55 Fruit Street, Boston, Massachusetts 02114-2696. E-mail: Sgrinspoon partners.
More rofecoxib and celecoxib users had previously undergone upper gastrointestinal diagnostic procedures or received gastroprotective agents than the other groups table 1. Celecoxib celebrex indicationGrandmother, as well as two maternal aunts. She had no siblings. Her physical examination revealed an obese female, asleep but easily awakened, breathing comfortably at 24 respirations per minute. Her temperature was 36.9 C, pulse 131, blood pressure133 74 mm Hg. She weighed 120 kg, height was 162.7 cm, and body mass index was 45.3. She had severe acanthosis nigricans involving her neck, axillae, umbilicus, and groin with many skin tags on her neck. She had no evidence of retinopathy. Her mucus membranes were dry. Her lungs were, clear and her cardiac examination was normal except for tachycardia. She. Synopsis According to a report in the Archives of Internal Medicine, at equally effective doses for osteoarthritis, treatment with rofecoxib but not celecoxib or naproxen induced a significant increase in 24-hour systolic BP. The Celecoxib Rofecoxib Efficacy and Safety in Comorbidities Evaluation Trial CRESCENT ; randomised patients to treatment with 200 mg d of celecoxib n 136 ; , 25 mg d rofecoxib n 138 ; , or 500 mg of naproxen twice daily n 130 ; for 12 weeks. Twenty-fourhour ambulatory BP monitoring and arthritis efficacy assessments were conducted at randomisation and at weeks 6 and 12 of treatment. The primary end point was the mean change from baseline in average 24-hour systolic BP at week 6. The following results were reported: Similar reductions in osteoarthritis symptoms pain, mobility, and stiffness ; in all treatment groups. Mean 24-hour systolic BP following 6 weeks of therapy was increased significantly by rofecoxib from 130.3 to 134.5 mm Hg; P 0.001 ; but not by celecoxib 132 to 131.9 mm Hg; P 0.54 ; or naproxen 133.7 to 133 mm Hg; P 0.74 ; . The BP difference between rofecoxib and celecoxib was 3.78 mm Hg 95% CI, 1.18-6.38; P 0.005 ; and between rofecoxib and naproxen, 3.85 mm Hg 1.15-6.55; P 0.005 ; . The proportion of patients with controlled hypertension at baseline who developed ambulatory hypertension by week 6 24-hour systolic BP 135 mm Hg ; was significantly greater with rofecoxib 30% ; than with celecoxib 16% ; P 0.05 ; but not significantly greater than with naproxen 19.
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