Clinicians routinely monitor drug pharmacodynamics by directly measuring the physiological indices of therapeutic responses, such as lipid concentrations, blood glucose, blood pressure, and clotting [Anyone involved in the utilization of information derived from TDM must always bear in mind that the interpretation of plasma drug concentration must always be carried out in conjunction with an assessment of the clinical status of the patient.

A concentration outside of the range also does not indicate that a patient will experience toxicity or reduced efficacy; however, the likelihood of either is certainly lower [The process of selecting the most appropriate dosage regimen to achieve concentrations in a relatively narrow range may be complicated by unpredictable intrapatient and interpatient variability in the drug’s pharmacokinetics. MPA is metabolized to its glucuronide metabolite, MPA glucuronide (MPAG), by glucoronyl transferases in the liver and possibly elsewhere. Until the mid-1990s, CsA and azathioprine were the cornerstones in maintenance immunosuppressive therapy. Some of the factors include drug-nutrients interactions, drug-disease interactions, renal insufficiency, inflammation and infection, gender, age, polymorphism and liver mass.

It is an imidazolyl derivative of 6-mercaptopurine. Several studies have demonstrated that grapefruit juice can increase plasma concentrations of CsA by inhibiting CYP3A-mediated metabolism and by increasing drug absorption via inhibition of P-glycoprotein (P-gp) efflux transporters.

This chapter is distributed under the terms of the Help us write another book on this subject and reach those readersLogin to your personal dashboard for more detailed statistics on your publications.By Hung Do Nguyen, Rebecca Lucy Williams, Germaine Wong and Wai Hon LimWe are IntechOpen, the world's leading publisher of Open Access books. The depletion of lymphocytes is so marked that it takes several months or up to one year postadministration for a patient’s immune system to be fully reconstituted ([Alemtuzumab’s mechanism of depletion is so profound that its adverse-effect profile occurs frequently and with a high level of severity. Because of its high lipophilicity, CsA enters cells easily to gain access to the site of action [The principal side effects to CsA therapy are hypertension, nephrotoxicity, tremor, hirsutism, hyperlipidemia, nausea and vomiting, gingival hyperplasia, and hepatotoxicity [Sites of action of immunosuppressive agents on T-cell activation [Administration of CsA adversely affects plasma lipoprotein and cholesterol levels causing hyperlipidemia [TRL (Prograf®) is a macrolide antibiotic produced by The compound is chemically distinct from CsA but both agents elicit similar immunosuppressant effects. As PhD students, we found it difficult to access the research we needed, so we decided to create a new Open Access publisher that levels the playing field for scientists across the world. DOI: …

In transplant recipients, both supratherapeutics and subtherapeutics drug concentrations can have devastating results. It is it known that neurological and gastrointestinal side effects occur more frequently at higher concentrations of TRL [Immunosuppressants display significant interindividual variability in plasma drug concentrations, which creates the demand for TDM when such drugs are used.

Daclizumab consists of 90% human and 10% murine components. << /D [ 3 0 R /XYZ null 629.5473 null ]

/Length 17 0 R The increased number of samples required, makes AUC monitoring impractical for routine clinical use, more expensive in the short term because of increased sample collection, analysis and interpretation of results, and inconvenient for patients, especially those in an outpatient setting [This approach, which is termed ‘absorption profiling’, has the underlying rationale that the 4-hour absorption phase following administration provides measurements that are more informative than CThe initial pharmacokinetic models for CsA were complicated by the nonlinear, segmented, zero order absorption of the drug from the gut [The therapeutic range for TRL used by most transplantation centers is 5–20 ng/mL in blood.

Sirolimus (previously known as rapamycin), a macrocyclic lactone, is a potent immunosuppressive agent.

Renal insufficiency can result in an altered free fraction of MPA due to the reduction in protein binding. Although the current labeling information for MMF does not indicate any need for therapeutic monitoring of plasma MPA concentrations, there were a number of studies showing a relationship between MPA pharmacokinetics and clinical outcome [The incorporation of MMF into immunosuppressive regimens has been associated with decrease rates of acute rejection and decreased chronic allograft loss. The antagonistic effect on the IL-2 receptor prevents T-cell activation and subsequent proliferation without causing lysis or cell destruction. Like CsA, TRL inhibits Tcell activation by inhibiting calcineurin [TRL is an established immunosuppressant for the prevention and treatment of allograft rejection in organ transplantation. T cells are inhibited from making IL-2 and proliferating. therapeutic drug monitoring of antirejection agents is essential for designing an effective immunosuppressive protocol for individual solid organ transplant recipients.

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