The pharmacokinetics of mycophenolate mofetil in Thai kidney transplant recipients. 2004

S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
Ramathibodi Hospital, Bangkok, Thailand. rasja@mahidol.ac.th

Mycophenolate mofetil, in addition to cyclosporine and prednisolone significantly reduces the rate of acute rejection. The original recommended dose of MMF is fixed at 2 g/day. However, Thai patients cannot tolerate this dose due to gastrointestinal adverse effects. So the majority of patients are maintained on MMF at doses ranging from 0.5 to 2 g/day, according to their tolerability with an acceptable rate of acute rejection episodes. This study sought to determine the steady state pharmacokinetics of MMF in Thai kidney transplant recipients on stable doses of MMF. Forty-six kidney transplant patients more than 3 months on a stable MMF dose of 0.5, 1, 1.5, and 2 g/day together with cyclosporine and prednisolone underwent a single pharmacokinetic blood sampling for 12 hours following the morning dose of MMF. The analysis of plasma concentrations of mycophenolic acid (MPA), the sole pharmacologically active metabolite of MMF, was performed by using an high performance liquid chromatography method. Sparse efficient sampling strategies were employed to optimize the blood sampling schedule. Hence, blood samples were collected at 0, 0.5, 2, 12 hours after the MMF dose. The sampling time was designed to best estimate AUC(0-tau) at steady state. The initial MPA-Bayesian estimator were used for MPA concentrations that would allow the best estimation of Vc, CLt, and Ka. In this study, there is a high interindividual variability in the AUC. The median MPA AUC was 34.3 ug.h/mL (range 14.1-65.4). Thirty-one of 45 (68.9%) patients had a MPA AUC within 20 to 40 ug.h/mL, which is the most reasonable risk: benefit ratio in terms of preventing acute rejection episodes. Forty-one of 45 (91.1%) patients had MPA AUC within 20 to 60 ug.h/mL, which is the MPA therapeutic range. The highest Pearson correlation coefficient of determination between MPA AUC and a single concentration was observed with MPA 2 hours (r = 0.622) Without a fixed dosing regimen, most Thai kidney transplant recipients who receive MMF as part of a maintenance immunosuppressive regimen have the MPA AUC within the therapeutic window. The single drug concentration that correlates well with the AUC is MPA at 2 hours postdose.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009173 Mycophenolic Acid Compound derived from Penicillium stoloniferum and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase (IMP DEHYDROGENASE). Mycophenolic acid exerts selective effects on the immune system in which it prevents the proliferation of T-CELLS, LYMPHOCYTES, and the formation of antibodies from B-CELLS. It may also inhibit recruitment of LEUKOCYTES to sites of INFLAMMATION. Cellcept,Mycophenolate Mofetil,Mycophenolate Mofetil Hydrochloride,Mycophenolate Sodium,Mycophenolic Acid Morpholinoethyl Ester,Myfortic,RS 61443,RS-61443,Sodium Mycophenolate,Mofetil Hydrochloride, Mycophenolate,Mofetil, Mycophenolate,Mycophenolate, Sodium,RS61443
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D013785 Thailand Formerly known as Siam, this is a Southeast Asian nation at the center of the Indochina peninsula. Bangkok is the capital city. Kingdom of Thailand,Siam

Related Publications

S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
January 1998, Advances in experimental medicine and biology,
S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
August 2019, International journal of clinical pharmacy,
S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
September 2007, Transplantation proceedings,
S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
November 2007, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society,
S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
June 2007, Therapeutic drug monitoring,
S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
January 1998, Transplant international : official journal of the European Society for Organ Transplantation,
S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
March 2005, Transplantation proceedings,
S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
November 2007, Clinical journal of the American Society of Nephrology : CJASN,
S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
January 2018, Frontiers in pharmacology,
S Jirasiritham, and V Sumethkul, and V Mavichak, and K Na-Bangchang
March 1998, International journal of clinical pharmacology and therapeutics,
Copied contents to your clipboard!