Clinical Pharmacokinetics and Pharmacodynamics of Mycophenolate in Solid Organ Transplant Recipients
Myocphenolate is one of the most commonly used antimetaboilte immunosuppressants that is currently available. It is primarily used as part of treatment for those patients who receive an organ transplnat.
The active ingredient in myocphenolates is mycophenolic acid, and there are currently two compounds that are available (mycophenolate mofetil (MM) and enteric-coted mycophenolate sodium (EC)). The reason that mycophenolic acid is the drug of choice for organ transplants is because it is a selective and reversible inhibitor of inosine monophospate dehydrogenase, which leads to the eventual arrest of T- and B-lymphocyte proliferation.
MM and EC are hydrolysed to mycophenolic acid by esterases located in the intestinal wall, blood, liver and other tissues throughout the body. The oral bioavailavilty of mycophenolic acid after dosing with MM ranges from 80.7% to 94%, while after dosing with EC the absolute bioavailavilyt of mycophenolic acid is approximately 72%.
Myocophenolic acid binds 97-99% to serum albumin in patients who have normal renal and liver function, it is metabolized in the liver, intestine, and kidneies by uridine diphosphate gluconosyltransferases.
When used in conjunction with ciclosporin (another iimmunosuppressant ) MM produced mycophenolic acid levels 30-40% lower than when used in alone or in combinations with other immunosuppressing agents. It is suggested that high doses of corticosteroids my induce the expression of uridine diphosphate gluconosyltransferases, which would effectively reduce the reduce the patient's exposure to mycophenolic acid. It has aso been found that other medications can interfere with the absorption, such as enterohepitc recycling and the metabolism of mycophenolte. For undescribed reasons most of the parmacokinetic investigations of mycophenolic acid have been with the use of MM instead of EC.
It has been found that patient body weight, serum albumen concentrations and immunosuppressant co-therapy have a significant influence on the apparent oral clearance of mycophenolic acid. Oral clearance means the rate of clearance of drugs that are administered orally.
The majority of data collected on mycophenolic acid has been obtained from patients who have not only received MM, but was done within the first year of a renal transplant. I personally feel that this tends to bias the findings of any study since it only takes into account one drug and one organ system, but I can only present on the information that is at hand.
Low levels of mycophenolic acid in circulation after 24 hours has been associated with increased incidences of "biopsy-proven rejection," but gastrointestinal events may be related to the administered dose. On the other end of the spectrum high levels of mycophenolic acid in circulation have been shown to be associated with leukopenia and anaemia in some studies. By keeping track of the levels of mycophenolic acid in circulation for the first 12 hours the risk of rejection and toxicity have been shown to be reduced. It is important that each patient be treated with indivudualism, as each case is different, so dosing should be done accordingly.
I selected this article because while I was working at the Texas Heart Institute I actually learned quite a bit about kidney transplants, so I wanted to look a little further into organ transplantation.
url:
http://web.ebscohost.com/ehost/pdfviewer/pdfviewer?sid=31c1d7d8-1cc3-4a27-bd00-52f4243bb1eb%40sessionmgr11&vid=2&hid=25
The active ingredient in myocphenolates is mycophenolic acid, and there are currently two compounds that are available (mycophenolate mofetil (MM) and enteric-coted mycophenolate sodium (EC)). The reason that mycophenolic acid is the drug of choice for organ transplants is because it is a selective and reversible inhibitor of inosine monophospate dehydrogenase, which leads to the eventual arrest of T- and B-lymphocyte proliferation.
MM and EC are hydrolysed to mycophenolic acid by esterases located in the intestinal wall, blood, liver and other tissues throughout the body. The oral bioavailavilty of mycophenolic acid after dosing with MM ranges from 80.7% to 94%, while after dosing with EC the absolute bioavailavilyt of mycophenolic acid is approximately 72%.
Myocophenolic acid binds 97-99% to serum albumin in patients who have normal renal and liver function, it is metabolized in the liver, intestine, and kidneies by uridine diphosphate gluconosyltransferases.
When used in conjunction with ciclosporin (another iimmunosuppressant ) MM produced mycophenolic acid levels 30-40% lower than when used in alone or in combinations with other immunosuppressing agents. It is suggested that high doses of corticosteroids my induce the expression of uridine diphosphate gluconosyltransferases, which would effectively reduce the reduce the patient's exposure to mycophenolic acid. It has aso been found that other medications can interfere with the absorption, such as enterohepitc recycling and the metabolism of mycophenolte. For undescribed reasons most of the parmacokinetic investigations of mycophenolic acid have been with the use of MM instead of EC.
It has been found that patient body weight, serum albumen concentrations and immunosuppressant co-therapy have a significant influence on the apparent oral clearance of mycophenolic acid. Oral clearance means the rate of clearance of drugs that are administered orally.
The majority of data collected on mycophenolic acid has been obtained from patients who have not only received MM, but was done within the first year of a renal transplant. I personally feel that this tends to bias the findings of any study since it only takes into account one drug and one organ system, but I can only present on the information that is at hand.
Low levels of mycophenolic acid in circulation after 24 hours has been associated with increased incidences of "biopsy-proven rejection," but gastrointestinal events may be related to the administered dose. On the other end of the spectrum high levels of mycophenolic acid in circulation have been shown to be associated with leukopenia and anaemia in some studies. By keeping track of the levels of mycophenolic acid in circulation for the first 12 hours the risk of rejection and toxicity have been shown to be reduced. It is important that each patient be treated with indivudualism, as each case is different, so dosing should be done accordingly.
I selected this article because while I was working at the Texas Heart Institute I actually learned quite a bit about kidney transplants, so I wanted to look a little further into organ transplantation.
url:
http://web.ebscohost.com/ehost/pdfviewer/pdfviewer?sid=31c1d7d8-1cc3-4a27-bd00-52f4243bb1eb%40sessionmgr11&vid=2&hid=25
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