Pharmacokinetics of mycophenolic acid after mycophenolate mofetil administration in liver transplant patients treated with tacrolimus

Ashokkumar Jain, Raman Venkataramanan, Imad S. Hamad, Sheila Zuckerman, Shimin Zhang, Jackie Lever, Vijay S. Warty, John J. Fung

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Abstract

The pharmacokinetics of mycophenolic acid (MPA) was studied after oral administration of mycophenolate mofetil (MMF) in 8 liver transplant patients. The mean (± SD) maximum MPA plasma concentration of 10.6 (± 7.5) mg/ml was achieved within 0.5 to 5 hours. The mean (± SD) steady-state area under the plasma concentration versus time curve (AUC0-12) was 40 (± 30.9) mg/ml/h. The mean (± SD) half-life was 5.8 (± 3.8) hours. There was poor correlation between trough blood concentrations of tacrolimus (r = -0.004) or serum creatinine (r = 0.689) with MPA AUC, while the serum bilirubin concentrations correlated (r = 0.743) well with MPA AUC, suggesting impairment in MPA conjugation in patients with liver dysfunction. The mean (± SD) ratio of the AUC of mycophenolic acid glucuronide (MPAG) to MPA was 64 (± 84), which correlated significantly with serum creatinine (r = 0.72) but not with serum bilirubin concentrations (r = 0.309), indicating accumulation of MPAG in patients with renal dysfunction. In 7 primary liver transplant patients on the same dose of MMF, the trough plasma concentrations of MPA during the first week of therapy ranged from < 0.3 to 1.5 μg/ml. The MPA concentrations increased by several folds during the next few weeks, which correlates well with increases in serum albumin concentrations. Changes in albumin appear to partially contribute to the variations in the pharmacokinetics of MPA in liver transplant patients.

Original languageEnglish (US)
Pages (from-to)268-276
Number of pages9
JournalJournal of Clinical Pharmacology
Volume41
Issue number3
DOIs
StatePublished - Jan 1 2001

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Mycophenolic Acid
Tacrolimus
Pharmacokinetics
Transplants
Liver
Area Under Curve
Serum
Bilirubin
Creatinine
Serum Albumin
Oral Administration
Half-Life
Liver Diseases
Albumins

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Jain, Ashokkumar ; Venkataramanan, Raman ; Hamad, Imad S. ; Zuckerman, Sheila ; Zhang, Shimin ; Lever, Jackie ; Warty, Vijay S. ; Fung, John J. / Pharmacokinetics of mycophenolic acid after mycophenolate mofetil administration in liver transplant patients treated with tacrolimus. In: Journal of Clinical Pharmacology. 2001 ; Vol. 41, No. 3. pp. 268-276.
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abstract = "The pharmacokinetics of mycophenolic acid (MPA) was studied after oral administration of mycophenolate mofetil (MMF) in 8 liver transplant patients. The mean (± SD) maximum MPA plasma concentration of 10.6 (± 7.5) mg/ml was achieved within 0.5 to 5 hours. The mean (± SD) steady-state area under the plasma concentration versus time curve (AUC0-12) was 40 (± 30.9) mg/ml/h. The mean (± SD) half-life was 5.8 (± 3.8) hours. There was poor correlation between trough blood concentrations of tacrolimus (r = -0.004) or serum creatinine (r = 0.689) with MPA AUC, while the serum bilirubin concentrations correlated (r = 0.743) well with MPA AUC, suggesting impairment in MPA conjugation in patients with liver dysfunction. The mean (± SD) ratio of the AUC of mycophenolic acid glucuronide (MPAG) to MPA was 64 (± 84), which correlated significantly with serum creatinine (r = 0.72) but not with serum bilirubin concentrations (r = 0.309), indicating accumulation of MPAG in patients with renal dysfunction. In 7 primary liver transplant patients on the same dose of MMF, the trough plasma concentrations of MPA during the first week of therapy ranged from < 0.3 to 1.5 μg/ml. The MPA concentrations increased by several folds during the next few weeks, which correlates well with increases in serum albumin concentrations. Changes in albumin appear to partially contribute to the variations in the pharmacokinetics of MPA in liver transplant patients.",
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Pharmacokinetics of mycophenolic acid after mycophenolate mofetil administration in liver transplant patients treated with tacrolimus. / Jain, Ashokkumar; Venkataramanan, Raman; Hamad, Imad S.; Zuckerman, Sheila; Zhang, Shimin; Lever, Jackie; Warty, Vijay S.; Fung, John J.

In: Journal of Clinical Pharmacology, Vol. 41, No. 3, 01.01.2001, p. 268-276.

Research output: Contribution to journalArticle

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AU - Jain, Ashokkumar

AU - Venkataramanan, Raman

AU - Hamad, Imad S.

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