Comparison of mycophenolic acid pharmacokinetic parameters in kidney transplant patients within the first 3 months post-transplant

Pawiński, Tomasz; Durlik, M.; Szlaska, Iwona; Urbanowicz, A.; Majchrnak, J.; Gralak, Beata

doi:10.1111/j.1365-2710.2006.00713.x

Cited by 45 publications

(27 citation statements)

References 30 publications

(40 reference statements)

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“…The C max2 observed in 26 patients (84%) between 1.5 and 10 hours after dosing may be attributed to the enterohepatic recirculation. 17 The t max2 reported from 2 similar surveys in Iran (range, 6-10 h) 18,19 were within the range observed in the present study.…”

Section: Resultssupporting

confidence: 76%

“…14,17 The AUC of only 8 patients (26%) in the present study were within the therapeutic range. In contrast with the current findings, our previous study on 21 kidney transplant recipients at 3 months after transplant showed that the MPA AUC of 17 patients (81%) ranged from 30 to 60 mgh/L (unpublished data).…”

Section: Therapeutic Drug Monitoring Of Mmf Early After Transplant Mamentioning

confidence: 91%

“…15 Several studies in kidney transplant recipients have demonstrated that the mean total MPA AUC is 30% to 50% lower in the first few weeks after transplant than at 2 to 6 months after transplant. 17,22 Considering renal function early after transplant (normal versus impaired), not more than 22% increase in the AUC of total MPA is detected. 23 The lower MPA AUC in the early than later periods after transplant could be, in part, a result of a pharmacokinetics drug interaction between MMF and cyclosporine.…”

Section: Therapeutic Drug Monitoring Of Mmf Early After Transplant Mamentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 76%

Section: Therapeutic Drug Monitoring Of Mmf Early After Transplant Mamentioning

confidence: 91%

Section: Therapeutic Drug Monitoring Of Mmf Early After Transplant Mamentioning

confidence: 99%

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Mycophenolic Acid Pharmacokinetics Early After Kidney Transplant

Honarbakhsh

Rouini²,

Lesanpezeshki³

et al. 2013

Exp Clin Transplant

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“…However, in renal transplant patients that receive CsA in combination with MMF adequate plasma levels of MMF can be achieved in contrast to HSCT recipients. 26 Possibly this difference is due to higher CsA levels used in HSCT. Though, in a recent HSCT study no significant difference in MMF bioavailability could be observed between patients with CsA troughs X300 versus o300 ng/ml.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of oral mycophenolate mofetil in combination with CsA in dogs after nonmyeloablative allogeneic hematopoietic stem cell transplantation

Lange

Mueller

Altmann

et al. 2007

Bone Marrow Transplant

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Mycophenolate mofetil (MMF) has been used successfully in solid organ transplantation (SOT) and more recently in nonmyeloablative hematopoietic stem cell transplantation (HSCT) for prophylaxis of graft rejection and acute graft-versus-host disease. However, the pharmacokinetics of MMF seem to differ when applied in HSCT compared to SOT. Here, we analyzed pharmacokinetics of mycophenolic acid (MPA), the active metabolite of MMF, in a nonmyeloablative canine HSCT model. Dogs received nonmyeloablative TBI for conditioning followed by leukocyte antigen-identical littermate HSCT and immunosuppression containing cyclosporin A (CsA) and different doses of MMF. Pharmacokinetics were performed on days 2, 14 and 27. Dose escalation of MMF from 10 to 30 mg/kg tended to increase area under the curve (AUC) and the apparent oral clearance by 45 and 110%, respectively. Doses applied had no linear association with MPA concentration or blood trough level. No significant drug accumulation occurred over time. Using a twice daily MMF regimen, we conclude that an AUC of 30-60 lg/ml h as recommended for SOT cannot be reached in HSCT. Toxicities did not permit single doses higher than 30 mg/kg. Thus, if larger AUCs are desired in order to assure sufficient immunosuppression in HSCT, MMF might have to be administered at least three times daily.

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“…Tacrolimusbased treatment requires a lower dosage of MMF compared with a cyclosporine-based regimen to maintain the similar MPA plasma levels. (Pawinski et al, 2006).…”

Section: Wwwintechopencommentioning

confidence: 99%

Clinical Pharmacokinetics of Triple Immunosuppression Scheme in Kidney Transplant (Tacrolimus, Mycophenolate Mofetil and Corticosteroids)

Luisa¹,

Alejandro²

2011

Understanding the Complexities of Kidney Transplantation

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Comparison of mycophenolic acid pharmacokinetic parameters in kidney transplant patients within the first 3 months post-transplant

Abstract: The MPA AUC(0-12h) appeared to be the more effective PK parameter for predicting acute rejection. We recommend that routine MPA and MPAG therapeutic drug level monitoring should be an important part of MMF therapy.

Cited by 45 publications

References 30 publications

Mycophenolic Acid Pharmacokinetics Early After Kidney Transplant

Mycophenolic Acid Pharmacokinetics Early After Kidney Transplant

Pharmacokinetics of oral mycophenolate mofetil in combination with CsA in dogs after nonmyeloablative allogeneic hematopoietic stem cell transplantation

Clinical Pharmacokinetics of Triple Immunosuppression Scheme in Kidney Transplant (Tacrolimus, Mycophenolate Mofetil and Corticosteroids)

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