Therapeutic monitoring of mycophenolic acid

Shaw, Leslie M.; Nicholls, Andrew; Hale, Michael; Armstrong, Victor W.; Oellerich, Michael; Yatscoff, R.; Morris, Randall E.; Holt, David W.; Venkataramanan, Raman; Haley, Jane E.; Halloran, Philip F.; Ettenger, Robert B.; Keown, Paul; Morris, Raymond G.

doi:10.1016/s0009-9120(98)00040-x

Cited by 115 publications

(50 citation statements)

References 30 publications

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“…This target level was adapted from a consensus recommendation for therapeutic drug monitoring of MMF after solid organ transplantation. 16 The calculated dose was rounded to 250 mg intervals. The schedule of drug dosing and AUC measurements is summarized in Figure 1.…”

Section: Gvhd Prophylaxismentioning

confidence: 99%

Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation

Haentzschel¹,

Freiberg-Richter²,

Platzbecker³

et al. 2008

Bone Marrow Transplant

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As low trough levels of mycophenolic acid (MPA) have been measured in recipients of allo-SCTs, we performed a pilot study targeting mycophenolate mofetil (MMF) doses according to the MPA area under the concentration (AUC) levels. Twenty-nine patients were transplanted from matched sibling (n ¼ 7) and unrelated donors (n ¼ 22). Tacrolimus was given orally from day À1 to achieve trough blood levels of 5-10 ng/ml. MMF was started on day 0 at 1500 mg intravenously b.i.d. AUC measurements of MPA by HPLC were scheduled on days 3, 7 and 11 after transplantation. The MMF dose was modified to achieve an MPA AUC of 35-60 lg/ml/h. With the respective adjustments 66 and 75% surpassed the lower AUC target on days 7 and 11, respectively. The cumulative incidence of grade III-IV acute GVHD was 28% (8/29). Eight out of 24 evaluable patients (33%) suffer from limited (n ¼ 3) or extensive (n ¼ 5) chronic GVHD. Overall, the results of this study suggest that targeting of MPA exposure is feasible early after transplantation. A simplified MMF targeting strategy based on MPA C max or C 2h levels seems to be warranted in future trials involving more patients at later time points in the outpatient setting.

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Section: Gvhd Prophylaxismentioning

confidence: 99%

Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation

Haentzschel¹,

Freiberg-Richter²,

Platzbecker³

et al. 2008

Bone Marrow Transplant

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“…Mycophenolic acid (MPA) is the active metabolite of the registered prodrug mycophenolate mofetil (MMF) often used in combination with cyclosporin A (CsA) or tacrolimus (FK506) as an immunosuppressive agent after organ transplantation for the prophylaxis of acute rejection (Takahashi et al, 1995;Shaw et al, 1998). Following oral administration, MMF is completely absorbed and rapidly hydrolyzed to MPA by esterase present in the gut wall, liver, and possibly lung and peripheral tissues (Bullingham et al, 1996a).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of mycophenolic acid in Chinese kidney transplant patients

Huang

Sheng-Tu

et al. 2005

J. Zhejiang Univ. Sci.

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Abstract:To assess the influence of cyclosporin A (CsA) and tacrolimus (FK506) on mycophenolic acid (MPA) and correlation analysis of the pharmacokinetic parameters and patient characteristics, clinical outcome in Chinese kidney transplant recipients, the pharmacokinetics of 1000 mg mycophenolate mofetil (MMF) twice daily was measured by high-performance liquid chromatography (HPLC). PKS (Pharmaceutical Kinetics Software) 1.0.2 software package was used for the calculation of pharmacokinetic parameters. The mean C max , t max , and AUC (0−12) were (21.88±10.52) µg/ml, (1.20±0.95) h, and (52.546±13.215) µg·h/ml, respectively. The level of AUC (0−12) in the FK506 group was significantly higher than that in the CsA group. MPA appeared not to be affected by renal function. MPA AUC (0−12) showed statistically significant difference according to the patient's gender.

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“…MMF is currently being used for the prophylaxis of acute rejection in liver, kidney, heart, and lung transplantation (Shaw et al, 1998). Its mechanism of action involves the direct inhibition of inosine monophosphate dehydrogenase, thus preventing the proliferation of B and T lymphocytes (Lipsky, 1996).…”

mentioning

confidence: 99%

The Main Role of Ugt1a9 in the Hepatic Metabolism of Mycophenolic Acid and the Effects of Naturally Occurring Variants

Bernard¹,

Guillemette²

2004

Drug Metab Dispos

196

166

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ABSTRACT:Mycophenolic acid (MPA), a standard immunosuppressive drug, is characterized by unexplained highly variable pharmacokinetics in transplant recipients. The primary metabolic pathway of MPA is glucuronidation; however, literature reports are inconsistent and the contribution of all human UDP-glucuronosyltransferases (UGTs) has never been systematically assessed. Sixteen heterologously expressed UGTs were studied for MPA 7-O-glucuronidation and compared with liver, kidney, and intestine microsomes. For direct measurement of MPA and mycophenolic acid 7-O-glucuronide (MPAG), we used a liquid chromatography-mass spectrometry protocol. Metabolic studies demonstrated that the glucuronidation of MPA in humans occurs mainly in the liver at variable rates, as well as in the kidney and the intestine. Kinetic data normalized for UGT expression levels point to 1A8 and 1A9 as the main UGTs, as well as to lowactivity enzymes, 1A1, 1A7, and 1A10. According to their expression profiles, 1A8 and 1A9 are proposed, respectively, as the main extrahepatic and the only hepatic enzymes involved. The effects of naturally occurring 1A8 (*2 and *3) and 1A9 (*2 and *3) variants on MPA 7-O-glucuronidation were studied and data suggest that the C 277 Y of 1A8 and the M 33

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Therapeutic monitoring of mycophenolic acid

Cited by 115 publications

References 30 publications

Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation

Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation

Pharmacokinetics of mycophenolic acid in Chinese kidney transplant patients

The Main Role of Ugt1a9 in the Hepatic Metabolism of Mycophenolic Acid and the Effects of Naturally Occurring Variants

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