Clinical Pharmacokinetic and Pharmacodynamic Monitoring for Mycophenolate Mofetil

The use of mycophenolate mofetil (MMF), in combination with cyclosporine (CsA) or tacrolimus (FK) and corticosteroids, has been shown to improve clinical outcomes through significant reduction in the incidence of acute rejection in solid organ transplant patients. A fixed oral dosing regimen of 1 or 1.5 g MMF twice daily received Food and Drug Administration approval in 1995 with no recommendations for concentration monitoring at that time. Subsequent evidence has generated substantial debate on the need of clinical monitoring for MMF. This article summarizes the rationale, evidence, and approaches of clinical monitoring for MMF. Mycophenolic acid (MPA), the active moiety of MMF, noncompetitively inhibits the enzyme inosine monophosphate dehydrogenase (IMPDH), which is the target enzyme for MPA. Pharmacokinetic monitoring, by use of MPA predose or MPA area under the concentration-time curve (AUC) values, and pharmacodynamic monitoring by analysis of inhibition of IMPDH have been evaluated in organ transplant patients. The possibility of drug interactions between other immunosuppressive agents has also received attention recently. The clinical implications of drug interactions are discussed in this article.

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Surgical Considerations in Solid-Organ Transplant Recipients

DeckerMed Surgery ◽

10.2310/surg.2213 ◽

2015 ◽

Author(s):

Thomas A. Pham ◽

Marc L. Melcher

Keyword(s):

Immunosuppressive Agents ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Surgical Techniques ◽

Postoperative Management ◽

Solid Organ ◽

Medication Regimen ◽

Transplant Patients ◽

Transplant Center ◽

Number Of Patients

Advances in the management and the surgical techniques of solid-organ transplantation have led to a growing number of patients living longer with transplanted organs. Surgical intervention in these patients ideally should be carried out by the original transplant team; however, the goal of this review is to provide information for practicing surgeons who are not at a transplant center so that they may recognize transplant-related problems, to help decide when to perform an intervention or operation and when to consider transfer to a transplant center. With careful attention to medications and symptoms, general surgery principles will hold true with transplant patients. Minor procedures can usually be conducted without much modification, and major procedures may require some adjustment of the medication regimen. This review covers preoperative considerations, diagnostic and radiologic considerations, intraoperative considerations, management of perioperative infection, management of perioperative immunosuppression, postoperative management, when to consider transfer to a transplant center, special considerations, and annotated key references. Tables list anatomic and diagnostic details of abdominal organ transplants, and considerations for common immunosuppressive agents. This review contains 2 tables and 44 references

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Inhibitors of Calcineurin

Journal of Pharmacy Practice ◽

10.1177/0897190003260317 ◽

2003 ◽

Vol 16 (6) ◽

pp. 414-433

Author(s):

Curtis D. Holt ◽

Gordon Ingle ◽

Theodore M. Sievers

Keyword(s):

Adverse Effects ◽

Drug Interactions ◽

Immunosuppressive Agents ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Therapeutic Drug ◽

Solid Organ ◽

Transplant Recipients ◽

Organ Transplant Recipients ◽

Solid Organ Transplant Recipients

Before the early 1980s, patient and allograft survival for solid organ transplant recipients was dismal. By 1983, the first calcineurin blocker, cyclosporine (Sandimmun), had been introduced, and outcomes were dramatically improved. However, cyclosporine macroemulsion had suboptimal pharmacokinetics, significant drug interactions, and several adverse effects, including nephrotoxicity, neurotoxicity, hyperlipidemia, and hypertension. Recent advances with cyclosporine include the introduction of modified dosage formulations: Neoral, a microemulsion, and several generic microemulsion products. The potent second-generation calcineurin blocker tacrolimus (Prograf) was introduced in 1994 and has become the drug of choice for several types of transplant recipients. Although tacrolimus has improved pharmacokinetics and therapeutic drugmonitoring parameters, it has adverse effects such as nephrotoxicity, neurotoxicity, and diabetes. Thus, current immunosuppressive regimens implementing calcineurin blockers often involve additional immunosuppressive agents to “spare” the use of these agents, minimizing their adverse effects. This article reviews the mechanisms of action, pharmacokinetics, clinical use, therapeutic drug monitoring, drug interactions, adverse effects, and dosing of cyclosporine and tacrolimus in solid organ transplant recipients.

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Survey of Alternative Medicine Use among Organ Transplant Patients

Journal of Transplant Coordination ◽

10.1177/090591999700700307 ◽

1997 ◽

Vol 7 (3) ◽

pp. 123-130 ◽

Cited By ~ 3

Author(s):

Catherine C Crone ◽

Thomas N Wise

Keyword(s):

Drug Interactions ◽

Organ Transplant ◽

Herbal Medicines ◽

Food Supplements ◽

Solid Organ ◽

Health Food ◽

Transplant Patients ◽

Increased Risk ◽

Life Threatening ◽

Pharmacologically Active

Herbal medicine and health food supplements have become increasingly popular. However, many of these pharmacologically active compounds remain poorly understood. Patients with chronic and life-threatening conditions often use alternative therapies while receiving conventional medical care, and this population is at increased risk for complications and adverse drug interactions due to poor health and complex drug regimens. Patients awaiting or who had received solid organ transplants were surveyed about their use of herbal medicines and health food supplements. Twenty percent of respondents acknowledged experience with these products, which they used to prolong the function of a failing organ or to obtain relief from fatigue and insomnia. Transplant staff often were unaware of their patients' use of these treatments, despite patients' claims to the contrary. The potential for unexpected drug interactions, toxicity, and other adverse reactions resulting from the use of herbal medicines or supplements must be recognized and identified by transplant teams.

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