Buy Celebrex (Celecoxib)
Buy Celebrex Online
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PHARMACOLOGICAL PROPERTIES: the mechanism of action of celecoxib is in inhibition of prostaglandin synthesis, mainly through oppression of the COX-2. At therapeutic concentrations in humans celecoxib does not provide inhibiting action on COX-1. COX-2 is activated in response to the selection of mediators of the inflammatory process. The increased activity of the enzyme leads to the synthesis and accumulation of prostanoids of the inflammatory process, first of all prostaglandin E2, which cause inflammation, swelling and pain. Celecoxib has anti-inflammatory, analgesic and antipyretic activity, blocking the production of inflammatory prostanoids by the oppression of the COX-2. In animal studies celecoxib reduced the incidence and the number of tumors of the large intestine.
The studies in vivo and ex vivo found that celecoxib has a very low affinity for the constitutively expressed COX-1. Thanks to this celecoxib in therapeutic doses does not affect the synthesis of prostanoids, which occurs when the activation of the COX-1 and, respectively, on the physiological COX-1-dependent processes in the tissues, especially in the stomach, the intestines, and platelets.
Osteoarthritis and rheumatoid arthritis. Celecoxib able to reduce the severity of pain in the joints, their stiffness and swelling, as well as to improve the function of the joints in patients with osteoarthritis and rheumatoid arthritis. Celecoxib in the dose of 100 or 200 mg two times per day in patients with osteoarthritis significantly reduced the severity of pain already in 24-48 hours after the first dose. The effectiveness of the drug in the dose of 200 mg / day does not depend on the use of it in one or two reception.
Pain control, including in the primary dismenoree. Celebrex effectively reduced the severity of the pain (from moderate-to-vigorous) after maxillofacial and orthopedic surgical interventions and in the primary dismenoree. Decrease of severity of pain occurs in 1 h after application of the preparation.
Ankylosing spondylitis. When used at a dose of 100 mg twice a day, 200 mg 1 time a day and 400 mg 1 time per day celecoxib significantly reduced the intensity of the pain, the activity of the pathological process and improved functional capacity in patients with ankylosing spondylitis in the treatment for 6-12 weeks. In general, the effectiveness of daily doses of 200 or 400 mg was almost the same, however, a positive effect on the dose of 400 mg / day observed in a large number of patients.
Family adenomatous polyposis. In the application of celecoxib in the dose of 400 mg twice per day as an additional event (in combination with endoscopic surveillance and surgical treatment) of the patients family adenomatous polyposis significantly decreased the number of polyps (the duodenum and colon) and their size. The use of celecoxib in the dose of 400 mg 2 times / day was effective and well postponed. The number of side effects in patients family adenomatous polyposis was the same as in patients with arthritis.
Endoscopic studies. The dependence between the frequency of gastroduodenal ulcers and the dose of celecoxib is not revealed. Incidence of gastroduodenal ulcers and their complications (gastrointestinal bleeding, perforation or stenosis) of the patients who used celecoxib, was statistically lower in comparison with patients, applying the NSAIDS such as acetylsalicylic acid, naproxen, diclofenac or ibuprofen.
Influence on the function of platelets. In healthy volunteers celecoxib in therapeutic doses and the dose of 600 mg twice a day (a dose, which is three times the therapeutic) had no effect on platelet aggregation and bleeding time.
Influence on the cardiovascular system. Security influence on the cardiovascular system was studied with the use of celecoxib in patients with sporadic adenomatous polyposis in the studies on the prevention of the occurrence of sporadic colon and rectum adenoma (SKA) and sporadic colorectal adenomatous polyposis (Scapa). In the study on the prevention of SKA, which lasted more than three years, it is established that the use of celecoxib dozozawisimo increased the risk of cardiovascular death, myocardial infarction or stroke compared with placebo. In the study on the prevention of Scapa there were no statistically significant differences in these indicators.
When comparing the incidence of cardiac complications in patients using celecoxib, and in the group of patients who used other non-selective NSAIDS, it was revealed, that in the long admission celecoxib incidence of nonfatal myocardial infarction has a tendency to increase, the common indicators of cardiac mortality were similar, and the frequency of cases of nonfatal stroke was significantly more low in comparison with the similar indicators in the application of other non-selective NSAIDS. When compared with a placebo, and with other NSAIDS simultaneous admission of acetylsalicylic acid does not affect these indicators.
Pharmacokinetics. Absorption. Celecoxib well absorbed when taken on an empty stomach; the concentration in the plasma of the blood reaches the maximum level in about 2-3 hours. Bioavailability to the reception inside in the form of capsules is 99% in comparison with the bioavailability of the suspension (optimal form for the reception inside). In the fasting state maximum plasma concentration (Cmax) and AUC proportional to dose when used in the dose to 200 mg twice a day; in the application of the drug in high doses increase of these indicators is less than proportional.
Distribution. Linking blood plasma proteins is not dependent on the concentration and amounts to about 97% at therapeutic concentrations. In the blood of the preparation practically is not bound to red blood cells.
The dependence on food. Eating (especially with a high content of fat) delays the absorption of celecoxib, leads to the increase of time of achievement of maximal concentration of approximately 4 hours and increases the bioavailability of approximately 20%.
Metabolism. Celecoxib is metabolized mainly with the participation of zitohroma P450 2C9. Three of its metabolite, which are contained in the plasma of human blood (primary alcohols and carboxylic acid derivative, conjugate glukuronida) are inactive on inhibition of the COX-1 and COX-2. The activity of cytochrome P450 2C9 is reduced in individuals with genetic polymorphism, which leads to reduced activity of this enzyme, such as homozygous polymorphism enzymes cyp2c9. The use of celecoxib in patients with known or expected reduced activity of cyp2c9 (based on the previous experience of the application of other cyp2c9 substrates) should be conducts caution (see. THE APPLICATION). Application you need to start with the lowest recommended dose.
The Selection. Excretion of celecoxib occurs mainly in the liver. In an unchanged condition in the urine excreted less than 1% of the dose. In reconsidering the application of elimination half-life is 12 hours, and klirens about 500 ml / min. With the re-admission equilibrium concentration in the plasma is achieved in a period of five days. Individual variability of parameters pharmacokinetics (AUC, maximum concentration, elimination half-life) is about 30%. In the steady state volume of distribution in adults healthy persons is approximately 500 l/70 kg, which indicates a wide distribution of celecoxib in the tissues. Preclinical studies suggest that the drug penetrates through GEB.
Special populations. Elderly patients. In patients over 65 years of age average values of maximum concentration and AUC increased by 1.5-2 times. This effect mainly depends on the mass of the body, not from age of the patient. The level of celecoxib was higher in patients with lower body weight, so it can be increased in elderly persons having an average mass of the body in general lower than in young people. The older women noticed a trend toward a higher concentration of the drug in plasma compared to men of the same age. Any correction doses if this is not usually required. However, the people of elderly age with a small weight (less than 50 kg) is recommended to start the treatment with the appointment of the drug in the minimum therapeutic dose.
The Race. The results of pharmacokinetic studies indicate that the AUC of celecoxib in persons of a negroid race approximately on 40% more, than in caucasians. The cause and clinical significance of this fact is not installed, so the parties a negroid race is recommended to start the treatment with a destination in the minimum therapeutic dose.
Violation of the functions of the liver. The concentration of celecoxib in patients with mild hepatic impairment (functional class AND on Child-Pugh) not essentially different from that of patients in the control group matched for age and sex. In patients with moderately severe disorders of liver function (functional class IN the Child-Pugh), the concentration of celecoxib in the blood plasma was approximately twice as high than in the control group. The usual daily dose of celecoxib in patients with moderate hepatic impairment should be reduced by approximately 50%.
Violations of kidney function. The volunteers of the elderly with age-related decline in glomerular filtration rate (GFR) (average GFR 65 ml/min/1.73 m2) and in patients with stable chronic renal insufficiency (GFR 35-60 ml/min/1.73 m 2) the pharmacokinetics celecoxib was similar to that of patients with normal renal function. A significant relationship between the level of creatinine in the serum (or creatinine clearance) and clearance of celecoxib is not revealed. The presence of severe renal failure shall not affect the clearance of celecoxib, since the main way of its elimination is the metabolism in the liver with the formation of active metabolites.
Effects on the kidneys. At the modern stage of the value of the COX-1 and COX-2 in renal physiology is understudied. Celecoxib reduces the excretion of pge2 rate and 6-keto-PGE1α metabolite (prostacyclin) with urine, but does not affect the level of thromboxane B2 (THV2) in the blood serum and the excretion of 11-dehydro-THV2 (metabolite of thromboxane) in the urine
The studies in vivo and ex vivo found that celecoxib has a very low affinity for the constitutively expressed COX-1. Thanks to this celecoxib in therapeutic doses does not affect the synthesis of prostanoids, which occurs when the activation of the COX-1 and, respectively, on the physiological COX-1-dependent processes in the tissues, especially in the stomach, the intestines, and platelets.
Osteoarthritis and rheumatoid arthritis. Celecoxib able to reduce the severity of pain in the joints, their stiffness and swelling, as well as to improve the function of the joints in patients with osteoarthritis and rheumatoid arthritis. Celecoxib in the dose of 100 or 200 mg two times per day in patients with osteoarthritis significantly reduced the severity of pain already in 24-48 hours after the first dose. The effectiveness of the drug in the dose of 200 mg / day does not depend on the use of it in one or two reception.
Pain control, including in the primary dismenoree. Celebrex effectively reduced the severity of the pain (from moderate-to-vigorous) after maxillofacial and orthopedic surgical interventions and in the primary dismenoree. Decrease of severity of pain occurs in 1 h after application of the preparation.
Ankylosing spondylitis. When used at a dose of 100 mg twice a day, 200 mg 1 time a day and 400 mg 1 time per day celecoxib significantly reduced the intensity of the pain, the activity of the pathological process and improved functional capacity in patients with ankylosing spondylitis in the treatment for 6-12 weeks. In general, the effectiveness of daily doses of 200 or 400 mg was almost the same, however, a positive effect on the dose of 400 mg / day observed in a large number of patients.
Family adenomatous polyposis. In the application of celecoxib in the dose of 400 mg twice per day as an additional event (in combination with endoscopic surveillance and surgical treatment) of the patients family adenomatous polyposis significantly decreased the number of polyps (the duodenum and colon) and their size. The use of celecoxib in the dose of 400 mg 2 times / day was effective and well postponed. The number of side effects in patients family adenomatous polyposis was the same as in patients with arthritis.
Endoscopic studies. The dependence between the frequency of gastroduodenal ulcers and the dose of celecoxib is not revealed. Incidence of gastroduodenal ulcers and their complications (gastrointestinal bleeding, perforation or stenosis) of the patients who used celecoxib, was statistically lower in comparison with patients, applying the NSAIDS such as acetylsalicylic acid, naproxen, diclofenac or ibuprofen.
Influence on the function of platelets. In healthy volunteers celecoxib in therapeutic doses and the dose of 600 mg twice a day (a dose, which is three times the therapeutic) had no effect on platelet aggregation and bleeding time.
Influence on the cardiovascular system. Security influence on the cardiovascular system was studied with the use of celecoxib in patients with sporadic adenomatous polyposis in the studies on the prevention of the occurrence of sporadic colon and rectum adenoma (SKA) and sporadic colorectal adenomatous polyposis (Scapa). In the study on the prevention of SKA, which lasted more than three years, it is established that the use of celecoxib dozozawisimo increased the risk of cardiovascular death, myocardial infarction or stroke compared with placebo. In the study on the prevention of Scapa there were no statistically significant differences in these indicators.
When comparing the incidence of cardiac complications in patients using celecoxib, and in the group of patients who used other non-selective NSAIDS, it was revealed, that in the long admission celecoxib incidence of nonfatal myocardial infarction has a tendency to increase, the common indicators of cardiac mortality were similar, and the frequency of cases of nonfatal stroke was significantly more low in comparison with the similar indicators in the application of other non-selective NSAIDS. When compared with a placebo, and with other NSAIDS simultaneous admission of acetylsalicylic acid does not affect these indicators.
Pharmacokinetics. Absorption. Celecoxib well absorbed when taken on an empty stomach; the concentration in the plasma of the blood reaches the maximum level in about 2-3 hours. Bioavailability to the reception inside in the form of capsules is 99% in comparison with the bioavailability of the suspension (optimal form for the reception inside). In the fasting state maximum plasma concentration (Cmax) and AUC proportional to dose when used in the dose to 200 mg twice a day; in the application of the drug in high doses increase of these indicators is less than proportional.
Distribution. Linking blood plasma proteins is not dependent on the concentration and amounts to about 97% at therapeutic concentrations. In the blood of the preparation practically is not bound to red blood cells.
The dependence on food. Eating (especially with a high content of fat) delays the absorption of celecoxib, leads to the increase of time of achievement of maximal concentration of approximately 4 hours and increases the bioavailability of approximately 20%.
Metabolism. Celecoxib is metabolized mainly with the participation of zitohroma P450 2C9. Three of its metabolite, which are contained in the plasma of human blood (primary alcohols and carboxylic acid derivative, conjugate glukuronida) are inactive on inhibition of the COX-1 and COX-2. The activity of cytochrome P450 2C9 is reduced in individuals with genetic polymorphism, which leads to reduced activity of this enzyme, such as homozygous polymorphism enzymes cyp2c9. The use of celecoxib in patients with known or expected reduced activity of cyp2c9 (based on the previous experience of the application of other cyp2c9 substrates) should be conducts caution (see. THE APPLICATION). Application you need to start with the lowest recommended dose.
The Selection. Excretion of celecoxib occurs mainly in the liver. In an unchanged condition in the urine excreted less than 1% of the dose. In reconsidering the application of elimination half-life is 12 hours, and klirens about 500 ml / min. With the re-admission equilibrium concentration in the plasma is achieved in a period of five days. Individual variability of parameters pharmacokinetics (AUC, maximum concentration, elimination half-life) is about 30%. In the steady state volume of distribution in adults healthy persons is approximately 500 l/70 kg, which indicates a wide distribution of celecoxib in the tissues. Preclinical studies suggest that the drug penetrates through GEB.
Special populations. Elderly patients. In patients over 65 years of age average values of maximum concentration and AUC increased by 1.5-2 times. This effect mainly depends on the mass of the body, not from age of the patient. The level of celecoxib was higher in patients with lower body weight, so it can be increased in elderly persons having an average mass of the body in general lower than in young people. The older women noticed a trend toward a higher concentration of the drug in plasma compared to men of the same age. Any correction doses if this is not usually required. However, the people of elderly age with a small weight (less than 50 kg) is recommended to start the treatment with the appointment of the drug in the minimum therapeutic dose.
The Race. The results of pharmacokinetic studies indicate that the AUC of celecoxib in persons of a negroid race approximately on 40% more, than in caucasians. The cause and clinical significance of this fact is not installed, so the parties a negroid race is recommended to start the treatment with a destination in the minimum therapeutic dose.
Violation of the functions of the liver. The concentration of celecoxib in patients with mild hepatic impairment (functional class AND on Child-Pugh) not essentially different from that of patients in the control group matched for age and sex. In patients with moderately severe disorders of liver function (functional class IN the Child-Pugh), the concentration of celecoxib in the blood plasma was approximately twice as high than in the control group. The usual daily dose of celecoxib in patients with moderate hepatic impairment should be reduced by approximately 50%.
Violations of kidney function. The volunteers of the elderly with age-related decline in glomerular filtration rate (GFR) (average GFR 65 ml/min/1.73 m2) and in patients with stable chronic renal insufficiency (GFR 35-60 ml/min/1.73 m 2) the pharmacokinetics celecoxib was similar to that of patients with normal renal function. A significant relationship between the level of creatinine in the serum (or creatinine clearance) and clearance of celecoxib is not revealed. The presence of severe renal failure shall not affect the clearance of celecoxib, since the main way of its elimination is the metabolism in the liver with the formation of active metabolites.
Effects on the kidneys. At the modern stage of the value of the COX-1 and COX-2 in renal physiology is understudied. Celecoxib reduces the excretion of pge2 rate and 6-keto-PGE1α metabolite (prostacyclin) with urine, but does not affect the level of thromboxane B2 (THV2) in the blood serum and the excretion of 11-dehydro-THV2 (metabolite of thromboxane) in the urine