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The effect of rofecoxib and diclofenac on blood picture in male patients
Mohammed Z.K. Al-Hayali*, Faris A. Ahmed. **
*Directorate of Health, Mosul. **Department of physiology, Ninevah college of Medicine University of Mosul.
Received: Accepted ٧.١.٢٠٠٨ ١٠.١٠.٢٠٠٧
ABSTRAT Objectives: To assess the effect of roficoxib and also the effect of diclofenac as a standard nonsteroidal anti-inflammatory drug (NSAD) on complete blood picture. mg/day ٢٥ male patients on roficoxib therapy at ٢٩ Methods: Complete blood picture was taken for male patients on roficoxib ١٥ consecutive days. Complete blood picture was also taken for ٢١-١٤ for consecutive days. Comparison was made between measurements ٢١-١٤ mg/day for ١٠٠ thearapy at of blood picture before and at the end of treatment by using Students paired t-test. Results: Roficoxib or diclofenac showed no significant changes in complete blood picture in the male patients in comparison with the measurements before treatment. Conclusion: Roficoxib or diclofenac has no significant effect on blood picture in patients when used for short term with moderate doses. Keywords: roficoxib, diclofenc, complete blood picture.
اﻟﺨﻼﺻﺔ ﻣﻘﺪﻣﺔ: ﻟﺪراﺳﺔ ﺗﺎﺛﻴﺮ ﻋﻘﺎر روﻓﻴﻜﻮآﺴﺐ ﻋﻠﻰ ﻓﺤﻮﺻﺎت اﻟﺪم اﻟﻜﺎﻣﻠﺔ آﺬﻟﻚ ﻟﺪراﺳﺔ ﺗﺎﺛﻴﺮ ﻋﻘﺎرداﻳﻜﻠﻮﻓﻴﻨﺎك آﻌﻘﺎر ﻗﻴﺎﺳﻲ ﻏﻴﺮ ﺳﺘﻴﺮودي ﻣﻀﺎد ﻟﻼﻟﺘﻬﺎﺑﺎت ﻋﻠﻰ ﻓﺤﻮﺻﺎت اﻟﺪم اﻟﻜﺎﻣﻠﺔ. اﻟﻄﺮق: اﺧﺬت ﻓﺤﻮﺻﺎت اﻟﺪم اﻟﻜﺎﻣﻠﺔ ﻟﺘﺴﻌﺔ وﻋﺸﺮﻳﻦ ﻣﺮﻳﺾ ﻣﻦ اﻟﺬآﻮر وﺗﺤﺖ ﻋﻼج روﻓﻴﻜﻮآﺴﺐ ﺑﺠﺮﻋﺔ ٢٥ ﻣﻠﻐﻢ ﻓﻲ اﻟﻴﻮم ﻟﻔﺘﺮة ١٤ -٢١ ﻳﻮم ﺑﺼﻮرة ﻣﺘﺘﺎﻟﻴﺔ. آﺬﻟﻚ اﺧﺬت ﻓﺤﻮﺻﺎت اﻟﺪم اﻟﻜﺎﻣﻠﺔ ﻟﺨﻤﺴﺔ ﻋﺸﺮ ﻣﺮﻳﺾ ﻣﻦ اﻟﺬآﻮر وﺗﺤﺖ ﻋﻼج داﻳﻜﻠﻮﻓﻴﻨﺎك ﺑﺠﺮﻋﺔ ١٠٠ ﻣﻠﻐﻢ ﻓﻲ اﻟﻴﻮم ﻟﻔﺘﺮة ١٤-٢١ ﻳﻮم ﺑﺼﻮرة ﻣﺘﺘﺎﻟﻴﺔ. اﺟﺮﻳﺖ اﻟﻤﻘﺎرﻧﺔ ﺑﺎﺳﺘﻌﻤﺎل اﺧﺘﺒﺎر t ﻟﻠﻌﻴﻨﺎت اﻟﻤﺘﺮاﺑﻄﺔ. اﻟﻨﺘﺎﺋﺞ: ﻟﻢ ﻳﻈﻬﺮ ﻋﻘﺎر روﻓﻴﻜﻮآﺴﺐ او ﻋﻘﺎر داﻳﻜﻠﻮﻓﻴﻨﺎك أي ﺗﻐﻴﻴﺮ ﻣﻌﻨﻮي ﻓﻲ ﻓﺤﻮﺻﺎت اﻟﺪم اﻟﻜﺎﻣﻠﺔ ﻓﻲ اﻟﻤﺮﺿﻰ اﻟﺬآﻮر ﻋﻨﺪ ﻣﻘﺎرﻧﺘﻬﺎ ﻣﻊ ﻧﺘﺎﺋﺞ ﻓﺤﻮﺻﺎت اﻟﺪم ﻗﺒﻞ اﺧﺬ اﻟﻌﻼج. اﻻﺳﺘﻨﺘﺎج: ﻻﻳﻮﺟﺪ ﺗﺎﺛﻴﺮ ﻟﻌﻘﺎر روﻓﻴﻜﻮآﺲ او ﻋﻘﺎر داﻳﻜﻠﻮﻓﻴﻨﺎك ﻋﻠﻰ ﻓﺤﻮﺻﺎت اﻟﺪم ﻟﻠﻤﺮﺿﻰ ﻋﻨﺪ اﺳﺘﻌﻤﺎﻟﻬﺎ آﻞ ﻋﻠﻰ ﺣﺪة وﻟﻔﺘﺮة ﻗﺼﻴﺮة وﺑﺠﺮﻋﺔ ﻣﺘﻮﺳﻄﺔ.
selective inhibitors offered logical ٢-COX ٢-ofecoxib is a specific cyclooxygenase inhibitor and its benifical action is choices to alliterate pain and inflammation with (٢-R (COX ٣.similar to the traditional nonsteroidal anti- fewer side effects inflammatory drugs (NSAIDs) indicating similar Diclofenac shows a high degree of anti- inflammatory, analgesic and antipyretic ١.analgesic and anti-inflammatory effects .٤.Clinical studies of rofecoxib have demonstrated activity efficacy equivalent to COX nonselective In comparison with refecoxib, diclofenac is a NSAIDs with lower rates of gastrointestinal tract potent relatively nonselective COX inhibitor in ,Clearly ٢.side effects like endoscopic ulcers
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٢٠٠٨ ,١.No ,٨&٧ .Irq J Pharm Vol addition diclofenac can reduce arachidonic acid Male patients were included, who complained ٥.bioavailability The haematological effects of traditional from simple pain like backache or joint pain. ٢١-١٤ NSAIDs induced two opposing actions, in one The duration of treatment was between hand, NSAIDs inhibited prostaglandins (PGS) days. The studied groups were divided into two patients ٢٩ mediated inhibition of cytokines there by groups. The first group included increasing stem cells and colony forming unit given rofecoxib (Inflaix, Ajanta Pharma Limited, mg/day), their ages ranged between ٢٥) ,(CFU) proliferation and differentiation, on the India) years). The ٨.٩±٣٦.٨ :years (mean±SD ٤٩-٢٩ other hand, NSAIDs inhibited PGS mediated patients given ١٥ stimulation of erythropoietin release and second group included consequently inhibiting the maturation of diclofenac sodium (voldic S.R., pharma. mg/day ١٠٠) ,(International co, Amman, Jordan ٦.erythrocyte line -٢٢ derived PGS play the potential role in sustained release), with age range between ٢-COX .(years ٦.٣±٣٥.٥ :mean±SD) ٤٤ the control of cytokines production and ml) was taken from ٢.٥) However, both Venous blood sample ٧.consequent haematopoiesi derived PGE may play a the participants by venipuncture. The blood was ٢-and COX ١-COX ml EDTA (ethylene diamine ٢.٥ placed in ٨.role in the control of erythrocyte maturation deficiency appears to inhibit the onset or tetraacetic acid) tubes. The samples were ٢-COX the rate of haematopoiesis under tension mixed well and placed on a mechanical shaker. conditions, but unlikely compromising The tests were done within the first hour after sample collection. Total white blood cell ٩.eventually full haematological recovery This study has been done to investigate the (WBC), platelets, differential WBC and effect of rofecoxib and diclofenac on complete reticulocyte counts were performed by using a Packed cell ١٢,١٣.blood picture in male patients. manual microscopic method volume (PCV) and haemoglobin (Hb) were Patients and methods measured by microhaematocrit and Drabkin's Westergren .١٢,١٣ This study was carried out in the department of solution methods, respectively .(١٤)Rheumatology and in the Haematology method was used for measurement of ESR laboratory at Al-Salam Hospital in Mosul city, under the Results ,٢٠٠٤ from January to July supervision of haematologists in the hospital. No significant changes were found in Hb Patients with rheumatological diseases or (haemoglobin), PCV (packed cell volume), post-operative pain were excluded from the reticulocyte, total and differential WBC, and study. In addition, erythrocyte sedimentation platelet count in patient treated with rofecoxib in comparison with those (٢٩-days (n ٢١-١٤ rate (ESR) test was made to exclude the for .(١ presence of other concurrent diseases. measurements before treatment ( Table ,No significant changes were found in Hb ١٠.٠ Complete blood picture was made at about ,Blood samples PCV, reticulocytes, total and differenetial WBC ١٠.a.m. to avoid diurnal variation were taken from patients while they were and platelet counts in patients treated with days in comparison with ٢١-١٤ found that diclofenac for ١١ sitting, since Penev and Kereshka .(position of patients affects complete blood these measurements before treatment (Table٢ picture.
.Blood picture of rofecoxib in patients before and after treatment .١ Table
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(٢٩=Means±SD (n Parameters Significance Before treatment After treatment NS ١٢.٦٥±١٤٠.١٤ ١١.٢٤±١٣٦.٨٦ (Hb (g/L NS ٠.٠٤±٠.٤٣ ٠.٠٥±٠.٤٣ (%) PCV
NS ٢.٠٨±٧.٠٢ ١.٩١±٧.١٠ L/١٠٩ × Total WBC cont Differential WBC count (%) NS ٨.٠٥±٦٦.١٠ ١٠.٠٦±٦٣.٦٦ Neutrophils NS ٧.٨٥±٣٠.٣١ ٩.٢٤±٣٣.٤٥ Lymphocytes NS ٠.٨٤±٠.٢٨ ١.٤٧±٠.٦٩ Monocytes NS ٣.٨٨±٣.٣١ ٣.٨٢±٢.٢١ Eosinophils L/١٠٩ Differential WBC absolute count x NS ١.٦٥±٤.٦٨ ١.٥٥±٤.٥٥ Neutrophils NS ٠.٧٤±٢.٠٨ ٠.٨٧±٢.٣٥ Lymphocytes NS ٠.٠٥±٠.٠٢ ٠.١١±٠.٠٥ Monocytes NS ٠.٣١±٠.٢٤ ٠.٢٥±٠.١٥ Eosinophils
NS ٤٨.٤١±٢٤٨.٢٨ ٤٢١.٨± ٢٤٠.١٧ L/١٠٩ Platelet count x ٠.٠٥ >NS, insignificant, P
.Blood picture of diclofenac patients before and after treatment .٢ Table Significance (٢٩=Parameters Means±SD (n Before treatment After treatment NS ١٠.٧٠±٧٤ .١٣٨ ١١.٢٨±١٤٠.٣٣ (Hb (g/L NS ٠.٠٣±٠.٤٢ ٠.٠٣±٠.٤٣ (%) PCV NS ٠.٧٦±٠.٧٨ ٠.٧٩±٠.٨٤ (%) Reticulocytes
NS ١.٦٧±٦.٩٨ ١.٥٦±٦.٣١ L/١٠٩ × Total WBC cont Differential WBC count (%) NS ٦.٨٤±٦٢.٤٧ ٨.٣٢±٦٥.٣٣ Neutrophils NS ٧.٨٣±٣٤.٦٧ ٧.٤٠±٣١.٦٠ Lymphocytes NS ٠.٩٠±٠.٣٣ ٠.٧٢±٠.٣٣ Monocytes NS ٣.٠٧±٢.٥٣ ٢.٧١±٢.٠٧ Eosinophils L/١٠٩ Differential WBC absolute count x NS ١.١٧±٤.٣٨ ١.٢٧±٤.١٨ Neutrophils NS ٠.٧١±٢.٣٩ ٠.٦٠±١.٩٦ Lymphocytes NS ٠.٠٦±٠.٠٢ ٠.٠٥±٠.٠٢ Monocytes NS ٠.٢٥±٠.١٩ ٠.١٧±٠.١٢ Eosinophils
NS ٦٨.١٢±٣١١.٣٣ ٧٥.١٨±٢٧٦.٦٧ Platelet count L/١٠٩ x ٠.٠٥>NS, insignificant, P
Discussion
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Raskin JB. Gastrointestinal effects of non -٣ In the rofecoxib treated patients, complete blood picture was not significantly different steroidal anti-inflammatory therapy. Am J .١٢s-١٠٦:٣s ;١٩٩٩ from pretreatment values. These results are in Med .Menasse R, Hedwall PR, Kraetz J et al -٤ These ١٥,١٦.agreement with other studies authors did not find any significant effect of pharmacological properties of diclofenac short-term use of rofecoxib on complete blood sodium and its metabolites. Scand J .١٦-٢٢:٥;١٩٧٨ inhibition in vitro and Rheumatol supp ٢-picture. However, COX -Furst, munster T. Nonsteroidal anti -٥ in vivo was associated with increased WBC count in the peripheral blood including inflammatory drugs, disease- modifying antirheumatic drugs, nonopioid analgesics ٧.granulocyte, monocytes and lymphocytes Accordingly, the short duration and moderate and drug used in gout. In katzung BG eds. dose might not be enough to significantly Basic and clinical pharmacology. New York: -٢٠٠١:٦٠٢ affect the blood picture. Lang Medical booked McGraw-Hill .٦٠٧ In this study, complete blood picture was not Kozubik A, Pospisil M, Viklicka S et al. Effect -٦ significantly different in diclofenac treated patients in comparison with the pretreatment of indomethacin on the proliferative and values. These results were in agreement with differentiation activity in the haemopoietic found that system of lethally irradiated mice after ١٧.Emery et al ١٧,١٨.other studies the haematological effect of diclofenac syngeneic bone marrow transplantation. .٤١٨٤٢٣ :٣٣;١٩٨٧ required long term use. Moreover, Hofer et Folia Biol .Hartel C, Puttkamer JV, Gallner F et al -٧ found that the effect of diclofenac on ١٩.al blood required the use of toxic doses. Thus, Dose-dependent lmmunomodulatory effects the short term duration and the moderate dose of acetylsalicylic acid and indomethacin in of diclofenac, in this study, might be human whole blood potential role of inhibition. Scand J Immun ٢-contributing factors for the lack of significant cyclooxygenase .٤٢٠-٦٠:٤١٢;٢٠٠٤ .effects on the blood picture .Rocca B, Secchierob P, Ranellettic et al -٨ Non-steroidal antiinflammatery drugs and selective inhibitors affect the function Modalation of the expression and activity of ٢-COX rather than proliferation of platelets where they cyclooxygenase in normal and accelerated :(١٠)٣١ ;٢٠٠٤ can change the haemostasis by tipping the erythropiesis. Exp Haematol .٩٣٤-٩٢٤ balance that is naturally occurring between the
.Lorenz M, Slaughter HS, Westott DM et al -٩ and (TXA٢) prothrombic thromboxine A٢ ٢٠ is essential for normal ٢-In Cyclooxygenase ..(anthithrombic prostacycline (PGI٢ fluorouracil induced-٥ addition, roficoxib diminished platelet recovery from ;١٩٩٩ aggregation and inhibited-mediated myelotoxicity in mice. Exp Haematol .١٥٠٢-٢٧:١٤٩٤ ٢١.thrombosis in vitro model of thrombosis .Statland BE, Winkel P, Harris SC et al -١٠ In conclusion, short term use of moderate dose of diclofenac or rofecoxib has no effect Evaluation of biologic sources of variation of on blood picture in patients suffering from leukocyte counts another hematologic miner pain. quantities using very precise automated -٤٨:(١)٦٩;١٩٧٨ analyzers. Am J Clin Pathol .٥٤ References Penev M, Kereshka P. Effect of body position -١١ ٢-Evert's B, Wahrborg P, Hedner T. COX -١ specific inhibitors- the emergence of a new on laboratory hematological indices. Vutr .٧٢-٦٩ :(٤)٢٧ ;١٩٩٩ class of analgesic and anti-inflammatory Boles ,Haen PJ. Principles of Hemalology. WCB -١٢ .٣٤٣-٢٠٠٠,١٩:٣٣١ drug. Clinc Rheumatol .٤٢٠-٢٠٠١:٢٦ ;Brooks P, Emery P, Evans JF, Fenner H et Dubuque -٢ Bain BJ, Bates I. Basic haematological -١٣ al. Interpreting the clinical significance of the techniques. In Lewis SM, Bain BJ, Bates I ١-differential inhibition of cyclooxygenase Rheumatology eds. Dacie and Lewis Practical .٢-and cyclooxygenase .٧٨٨-٢٨:٧٧٠;١٩٩٩ Mosul College of Pharmacy 11 ٢٠٠٨
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.Silverstein FE, Faich G, Goldstein JL et al -١٨ ٩th ed, London: Churchill,Haematology Gastrointestinal anti-inflammatory drug for .٣٠-١٩;٢٠٠١ Livingstone .Lewis SM. Miscellaneous tests. In Lewis osteoarthritis and rheumatoid arthritis -١٤ .١٢٥٥-٢٠٠٠,٢٨٤:١٢٤٧ SM, Bain BJ, Bates I eds. London: JAMA .Hofer M, Pospisil M, Pipalova I et al -١٩ .٥٢٨-٥٢٧;٢٠٠١ Churchill Livingstone Morrison BW, Fricke J, Brown J et al. The modulation haemopoietic radiation -١٥ optimal analgesic dose of rofecoxib. J Am response of mice by diclofenac in ;١٩٩٦ fractionated treatment. Physiol Res .١٧٣٧-١٣١:١٧٢٩;٢٠٠٠ Dent Assoc .٢٢٠-٢١٣:(٣)٤٥ Merk and Co. Vioxx prescribing information -١٦ .Mukherjec D, Nissen SE, Topol EJ et al -٢٠ .٢٠٠٣ ,inhibitors and cardiovascular risk ٢-Emery P, Zeidler H, Kvien et al. celecoxib COX -١٧ versus diclofenac in long term management we defend our data and suggest caution. .٩٦٤-٩٦٣ :(١١)٦٨ ;٢٠٠١ of rheumatoid arthritis: randomized double Clev Clinic J Med .Hemandez MR, Tonda R, Pino M et al -٢١ -٣٥٤:٢١٠٦;١٩٩٩ blind comparison. Lancet Evaluation of roficoxib on platelet function .٢١١١ in an in vitro model of thrombosis with circulating human blood. Eu J Clin Invest .٣٠٢-٢٩٧:(٤)٣٤;٢٠٠٤
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