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

Full 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.

Author information

Author/s: Miura, Masatomo (M); Satoh, Shigeru (S); Kagaya, Hideaki (H); Saito, Mitsuru (M); Inoue, Takamitsu (T); Tsuchiya, Norihiko (N); Suzuki, Toshio (T); Habuchi, Tomonori (T);

Affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol), published in Germany. (Language: eng)

Reference: 2009-Oct; vol 65 (issue 10) : pp 1047-53

Dates: Created 2009/09/17; Completed 2009/11/02;

PMID: 19730841, status: MEDLINE (last retrieval date: 11/2/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

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

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

Associated Chemicals: Enzyme Inhibitors (0) ; Immunosuppressive Agents (0) ; Tacrolimus (109581-93-3) ; Mycophenolic Acid (24280-93-1) ; Prednisolone (50-24-8) ; CYP3A5 protein, human (EC 1.14.14.1) ; Cytochrome P-450 CYP3A (EC 1.14.14.1)

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