No impact of age on dose-adjusted pharmacokinetics of tacrolimus, mycophenolic acid and prednisolone 1 month after renal transplantation.

Abstract

PURPOSE:

The purpose of the study was to assess the impact of age on the pharmacokinetics of immunosuppressive drugs.

METHODS:

One hundred and ten renal transplant recipients, including 12 elderly patients over 60 years of age, 57 middle-aged patients between 40 and 59 years and 41 young adult patients 20 to 39 years of age were studied. To evaluate dose-adjusted pharmacokinetics and cytochrome P450 (CYP) 3A5 pharmacogenetics, the concentrations of tacrolimus, mycophenolic acid (MPA), MPA glucuronide (MPAG) and prednisolone were measured at 1 month post-transplantation.

RESULTS:

There were no differences in dose (D) and body weight (BW)-adjusted pharmacokinetic parameters of tacrolimus among the three groups. D/BW-adjusted C(max), C(0) and AUC(0-12) values of tacrolimus were significantly greater in patients with the CYP3A5*3/*3 genotype than in those with the CYP3A5*1 allele in young and middle-aged patients as previously reported, but not in the elderly. There were no significant differences in the D-adjusted pharmacokinetics of prednisolone and MPA among the three groups.

CONCLUSION:

The aging process itself may have a small effect on the pharmacokinetics of tacrolimus, MPA, or prednisolone. However, a larger number of subjects need to be studied to confirm the impact of age on the CYP3A5 pharmacogenetics of tacrolimus in the elderly.

• Authors: Masatomo Miura, Shigeru Satoh, Hideaki Kagaya, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Toshio Suzuki, Tomonori Habuchi
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 65 Issue 10 Pg. 1047-53 (Oct 2009) ISSN: 1432-1041 [Electronic] Germany
• PMID: 19730841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Immunosuppressive Agents
• Prednisolone
• CYP3A5 protein, human
• Cytochrome P-450 CYP3A
• Mycophenolic Acid
• Tacrolimus

Topics

• Adult
• Age Factors
• Aged
• Aging
• Analysis of Variance
• Area Under Curve
• Body Weight
• Cytochrome P-450 CYP3A (drug effects, genetics, metabolism)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacokinetics)
• Female
• Genotype
• Humans
• Immunosuppressive Agents (administration & dosage, pharmacokinetics)
• Kidney Transplantation
• Male
• Middle Aged
• Mycophenolic Acid (administration & dosage, pharmacokinetics)
• Prednisolone (administration & dosage, pharmacokinetics)
• Tacrolimus (administration & dosage, pharmacokinetics)
• Time Factors