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The effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in adolescent kidney transplant recipients.
Med Sci Monit. 2008 May; 14(5):CR251-254.MS

Abstract

BACKGROUND

CYP3A5 gene polymorphism has been shown to influence tacrolimus (TAC) blood concentration and dose requirement in adult kidney transplant patients. The aim was to analyze retrospectively the modification induced by CYP3A5 gene polymorphism on TAC's pharmacokinetic parameters obtained from 26 adolescents receiving TAC as their main immunosuppressive drug.

MATERIAL/METHODS

The adolescent kidney transplant patients were genotyped for CYP3A5*3 and grouped accordingly. TAC dose, blood levels, and dose-normalized TAC blood concentration and volume of distribution obtained at different post-transplant periods during the first post-transplant year were correlated with the corresponding genotype.

RESULTS

During the first three months post-transplant, heterozygotes (CYP3A5*1/*3) displayed a lower TAC blood concentration than homozygotes (CYP3A5*3/*3) (at 1 month: 7.8+/-2.1 vs. 13.4+/-6 ng/ml, p=0.007) despite a therapeutic monitoring strategy. Between 3-12 months post-transplant, TAC blood concentration was comparable between the two groups, but a two-fold increase in the daily drug dose was necessary for the heterozygotes (at 6 months: 0.23+/-0.1 vs. 0.13+/-0.06 mg/kg, p=0.04). The dose-normalized TAC concentration [(ng/ml)/(mg/kg)] was significantly lower in patients displaying the CYP3A5*1/*3 polymorphism (at 2 weeks: 33+/-2.16 vs. 71.1+/-37.8, p=0.01; 6 months: 35.4+/-12.9 vs. 85.2+/-58.9, p=0.01). At the same time, the volume of distribution of the drug in the latter group was distinctly increased for the entire post-transplant year (at 6 months: 1.79+/-0.42 vs. 0.73+/-0.5 l/kg, p=0.001).

CONCLUSIONS

The great influence of CYP3A5 on the pharmacokinetics and pharmacodynamics of TAC in young transplant recipients suggests the need for pre-transplant screening of this polymorphism to improve TAC therapy.

Authors+Show Affiliations

Laboratory of Clinical Pathology, Maggiore Hospital Policlinico, Mangiagalli and Regina Elena Foundation, IRCCS, Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18443548

Citation

Tirelli, Silvia, et al. "The Effect of CYP3A5 Polymorphisms On the Pharmacokinetics of Tacrolimus in Adolescent Kidney Transplant Recipients." Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, vol. 14, no. 5, 2008, pp. CR251-254.
Tirelli S, Ferraresso M, Ghio L, et al. The effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in adolescent kidney transplant recipients. Med Sci Monit. 2008;14(5):CR251-254.
Tirelli, S., Ferraresso, M., Ghio, L., Meregalli, E., Martina, V., Belingheri, M., Mattiello, C., Torresani, E., & Edefonti, A. (2008). The effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in adolescent kidney transplant recipients. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 14(5), CR251-254.
Tirelli S, et al. The Effect of CYP3A5 Polymorphisms On the Pharmacokinetics of Tacrolimus in Adolescent Kidney Transplant Recipients. Med Sci Monit. 2008;14(5):CR251-254. PubMed PMID: 18443548.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in adolescent kidney transplant recipients. AU - Tirelli,Silvia, AU - Ferraresso,Mariano, AU - Ghio,Luciana, AU - Meregalli,Elisa, AU - Martina,Valentina, AU - Belingheri,Mirco, AU - Mattiello,Camilla, AU - Torresani,Emilio, AU - Edefonti,Alberto, PY - 2008/4/30/pubmed PY - 2008/8/12/medline PY - 2008/4/30/entrez SP - CR251 EP - 254 JF - Medical science monitor : international medical journal of experimental and clinical research JO - Med Sci Monit VL - 14 IS - 5 N2 - BACKGROUND: CYP3A5 gene polymorphism has been shown to influence tacrolimus (TAC) blood concentration and dose requirement in adult kidney transplant patients. The aim was to analyze retrospectively the modification induced by CYP3A5 gene polymorphism on TAC's pharmacokinetic parameters obtained from 26 adolescents receiving TAC as their main immunosuppressive drug. MATERIAL/METHODS: The adolescent kidney transplant patients were genotyped for CYP3A5*3 and grouped accordingly. TAC dose, blood levels, and dose-normalized TAC blood concentration and volume of distribution obtained at different post-transplant periods during the first post-transplant year were correlated with the corresponding genotype. RESULTS: During the first three months post-transplant, heterozygotes (CYP3A5*1/*3) displayed a lower TAC blood concentration than homozygotes (CYP3A5*3/*3) (at 1 month: 7.8+/-2.1 vs. 13.4+/-6 ng/ml, p=0.007) despite a therapeutic monitoring strategy. Between 3-12 months post-transplant, TAC blood concentration was comparable between the two groups, but a two-fold increase in the daily drug dose was necessary for the heterozygotes (at 6 months: 0.23+/-0.1 vs. 0.13+/-0.06 mg/kg, p=0.04). The dose-normalized TAC concentration [(ng/ml)/(mg/kg)] was significantly lower in patients displaying the CYP3A5*1/*3 polymorphism (at 2 weeks: 33+/-2.16 vs. 71.1+/-37.8, p=0.01; 6 months: 35.4+/-12.9 vs. 85.2+/-58.9, p=0.01). At the same time, the volume of distribution of the drug in the latter group was distinctly increased for the entire post-transplant year (at 6 months: 1.79+/-0.42 vs. 0.73+/-0.5 l/kg, p=0.001). CONCLUSIONS: The great influence of CYP3A5 on the pharmacokinetics and pharmacodynamics of TAC in young transplant recipients suggests the need for pre-transplant screening of this polymorphism to improve TAC therapy. SN - 1234-1010 UR - https://www.unboundmedicine.com/medline/citation/18443548/The_effect_of_CYP3A5_polymorphisms_on_the_pharmacokinetics_of_tacrolimus_in_adolescent_kidney_transplant_recipients_ DB - PRIME DP - Unbound Medicine ER -