Effect of Discontinuing Cyclosporine on Mycophenolic Acid Trough Levels in Kidney Transplant Recipients

Gregoor, P Jh Smak; Sévaux, R Gl de; Hené, R. J.; Hesse, C. J.; Hilbrands, Luuk B.; Vos, Pieter C.; Gelder, Teun van; Hoitsma, A.J.; Weimar, Willem

doi:10.1097/00007890-199904150-00816

Cited by 56 publications

(77 citation statements)

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“…In general, for the same MMF dose, MPA levels appear lower with CsA comedication and higher with Tac. 12,[23][24][25] Our study shows a significantly lower dose-normalized AUC 0-7 and a correspondingly higher dose-C 0 ratio in the CsAcomedicated group. A study of pediatric renal transplant recipients administered 600 mg/m 2 of MMF gave similar results, with a trend toward a lower dose-normalized AUC in those comedicated with CsA compared with those comedicated with Tac or without calcineurin inhibitors.…”

Section: Discussionmentioning

confidence: 47%

“…12 An additional study of adult renal transplant recipients found that MPA C 0 almost doubled at 9 months after transplantation after the discon- tinuation of CsA at 6 months. 23 Two possibilities have been suggested to underlie these drug interactions: (1) Tac augments the bioavailability of MMF through inhibition of MPA glucuronidation, the primary metabolic pathway for MPA 26 ; and (2) CsA inhibits enterohepatic recycling of MPA. 27 Our additional studies on the pharmacokinetics of mycophenolate glucuronide suggest both these mechanisms may apply and are reported elsewhere.…”

Section: Discussionmentioning

confidence: 99%

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Mycophenolic acid pharmacokinetics in pediatric liver transplant recipients

Brown

Itsuka

et al. 2003

Liver Transplantation

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The aim of this study is to study mycophenolic acid (MPA) pharmacokinetics in stable pediatric liver transplant recipients and determine which times best represent the area under the concentration versus time curve (AUC) of MPA plasma concentrations. MPA pharmacokinetic profiles were determined in 21 liver transplant recipients (age, 2 to 15 years; 12 boys) administered mycophenolate mofetil (MMF) for at least 6 months. Ten patients were coadministered cyclosporine A (CsA), and 11 patients were coadministered tacrolimus (Tac). Plasma MPA levels were analyzed by enzyme-multiplied immunoassay technique in blood samples at 0, 0.33, 0.67, 1.25, 2, 3.5, 5, and 7 hours after MMF administration. The AUC of plasma concentrations to 7 hours (AUC 0-7 ) was calculated using the linear trapezoidal rule. MPA plasma trough concentration (C 0 ), maximal concentration, and AUC 0-7 values ranged 9-to 14-fold at a median of 1.

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Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Mycophenolic acid pharmacokinetics in pediatric liver transplant recipients

Brown

Itsuka

et al. 2003

Liver Transplantation

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“…Further, it was shown that the pharmacokinetics of MPA is influenced by co-administration of calcineurin inhibitors such as CsA and FK506 (Bullingham et al, 1996a;Gregoor et al, 1999). Some changes in free MPA concentrations, due to patient characteristics such as severe renal impairment and gender, will lead to an altered efficacy or toxicity profile.…”

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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“…High doses of cyclosporine inhibit the enterohepatic recirculation of MPA. 24,25 In addition, protein binding changes with time after transplant, with the free fraction decreasing and total MPA concentrations increasing over time. This may decrease the MPA clearance and increase the MPA AUC.…”

Section: Therapeutic Drug Monitoring Of Mmf Early After Transplant Mamentioning

confidence: 99%

Mycophenolic Acid Pharmacokinetics Early After Kidney Transplant

Honarbakhsh

Rouini²,

Lesanpezeshki³

et al. 2013

Exp Clin Transplant

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Objectives: To determine the mycophenolic acid pharmacokinetic profile early after transplant in Iranian kidney graft recipients. Materials and Methods: A cross-sectional study was performed during 6 months in 31 patients who recently had kidney transplant and received fixed doses of mycophenolate mofetil (2 g/d). The plasma levels of mycophenolic acid were determined by high performance liquid chromatography. Results: The mean first mycophenolic acid peak level was 10 ± 5 mg/L. The mean mycophenolic acid area under the curve was 26 ± 19 mgh/L and apparent clearance was 57 ± 55 L/h. The mycophenolic acid area under the curve values of only 8 patients (26%) were within the therapeutic range (30-60 mgh/L). The first, second, and third mycophenolic acid peak levels correlated significantly with mycophenolic acid area under the curve (P < .05). Mycophenolic acid concentration at 10 hours had the highest correlation with mycophenolic acid area under the curve (r=0.962; P < .05). No statistically significant differences were evident in the mean mycophenolic acid area under the curve between men and women. Conclusions: There was a high degree of variation between different patients in mycophenolic acid pharmacokinetics early after kidney transplant.

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Effect of Discontinuing Cyclosporine on Mycophenolic Acid Trough Levels in Kidney Transplant Recipients

Cited by 56 publications

References 0 publications

Mycophenolic acid pharmacokinetics in pediatric liver transplant recipients

Mycophenolic acid pharmacokinetics in pediatric liver transplant recipients

Pharmacokinetics of mycophenolic acid in Chinese kidney transplant patients

Mycophenolic Acid Pharmacokinetics Early After Kidney Transplant

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