At doses that provide dramatic cytotoxic effect in two tests (determination of thymidine kinase in cells of mouse lymphoma and micronucleoli mouse) mycophenolate mofetil has the potential to cause chromosomal instability.
In animal oral drug studies at a dose of 0.5 times the systemic exposure dose of 2 g a day after a kidney transplant, and about 0.3 times the systemic exposure of the clinical dose of 3 g per day recommended after a heart transplant, caused malformations (including anophthalmia, agnates and hydrocephaly) in the first generation progeny, without toxic effects on the mother and fertility and reproduction of future generations.
In studies winstrol of teratogenicity in animals treated with the drug in a dose of systemic exposure approximately 0.5 times the dose of 3 g per day, there was resorption of fetuses and birth defects in rats (including anophthalmia, agnates and hydrocephaly) in the offspring rabbits were found malformations of the cardiovascular system, kidneys, ectopia of the heart and kidneys, diaphragmatic and umbilical hernia, no signs of toxic effects on the mother.
in toxicological studies of mycophenolate mofetil on the animals core lesions were located in the hematopoietic and lymphoid organs, and there is at this level of the system effects of the drug, which is equivalent to or less than the clinical exposure dose of 2 grams per day recommended to patients after kidney transplantation. Nonclinical toxicity profile of mycophenolate mofetil, coincides with the adverse events noted in clinical studies in humans, which allowed to obtain safety data more meaningful for the patient population.
The pharmacokinetic characteristics of winstrol have been studied in patients undergoing transplantation of kidney, heart and liver. In general, in patients after kidney transplantation and heart pharmacokinetic profile of winstrol same. In the early post-transplant period in patients undergoing liver transplantation and receiving MMF at a dose of 1.5 g, IFC concentration are the same as in patients after kidney transplantation, receiving at a dose of 1 g
Following oral administration is rapid and complete absorption and complete presystemic metabolism of mycophenolate mofetil with the formation of the active metabolite (mycophenolic acid). MMF Bioavailability after oral administration in accordance with the value (area under “concentration – time” curve) is, on average, 94% of that when it is administered intravenously. After oral administration the concentration mycophenolate mofetil not detected in the plasma.
In the early post-transplant period (up to 40 days after kidney transplant, heart or liver) average values were about 30% lower, and the maximum concentration – about 40% lower than in the late post-transplant period (3-6 months post-transplant).
food intake does not affect the extent of absorption of mycophenolate mofetil when administered at 1.5 g twice a day to patients after kidney transplantation. However, the maximum concentration of the winstrol while taking the drug during meals reduced by 40%.
Generally, about 6-12 hours after administration of the drug is observed secondary IFC increased concentration in the plasma, indicating that hepatic-intestinal drug recycling. When concomitant administration of cholestyramine AUC IFC is reduced by about 40%, indicating that the interruption of intestinal and hepatic circulation.
In clinically relevant concentrations IFC bound to plasma albumin at 97%.
After oral administration of radiolabelled mycophenolate mofetil 93% of the administered dose excreted in the urine and 6% – with the feces. Most (about 87%) of the administered dose is excreted in the urine in the form M. Small amounts of drug (<1% of the dose) are excreted in the urine as the .
Clinically defined by and concentration is not removed by hemodialysis. However, at higher concentrations MFKG (> 100 ug / ml) is some part of it can be removed. Sequestering bile acids such as cholestyramine reduce , interrupting the intestinal and hepatic recirculation.
Pharmacokinetics in specific clinical situations
In a study with a one-time drug intake in patients with severe chronic kidney disease higher than that in healthy volunteers and patients with less severe renal impairment. After receiving a single greater in patients with severe renal insufficiency, which is consistent with the known data of renal excretion
Studies on the repeated administration of mycophenolate mofetil with severe chronic renal impairment has not been carried out.
In patients with delayed renal graft function after transplant the average value is comparable to that of patients who began the graft function after transplantation without delay, and the average value was in plasma is 2-3 times more. patients with liver disease. in volunteers with alcoholic cirrhosis of the liver after oral administration revealed no changes in the pharmacokinetics and that indicates that damage to the liver parenchyma is not a contraindication for the purpose . Influence of hepatic pathology, this process is likely to depend upon the particular disease. In the case of liver disease with prevalence of lesions of the biliary tract (eg, primary biliary cirrhosis), the effect may be different. In patients elderly (≥ 65 years) The pharmacokinetics has not been studied.
Indications for use:
Prophylaxis of acute organ rejection and treatment of refractory to therapy, organ rejection in patients after allogeneic kidney transplant.
Prevention of acute organ rejection and improved graft survival and the survival of of the patients after allogeneic heart transplant.
Prevention Authority of acute rejection in patients after allogeneic liver transplantation.
CellCept is prescribed in the form of a combined therapy with cyclosporine and corticosteroids.
Increased individual sensitivity to CellCept, mycophenolic acid and other ingredients. Be wary – gastrointestinal disease (exacerbation).