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


CONCLUSIONS
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.
Miura
Masatomo
M
Department of Pharmacy, Akita University Hospital, Akita, Japan.
Satoh
Shigeru
S
Kagaya
Hideaki
H
Saito
Mitsuru
M
Inoue
Takamitsu
T
Tsuchiya
Norihiko
N
Suzuki
Toshio
T
Habuchi
Tomonori
T
D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging; D000704:Analysis of Variance; D019540:Area Under Curve; D001835:Body Weight; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011239:Prednisolone; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D009173:Mycophenolic Acid; D016559:Tacrolimus