Abstract

GUADARRAMA-DIAZ, Enrique Omar; GARCIA-ROCA, María Inés del Pilar; REYES-PEREZ, Herlinda  and  MEDEIROS, Mara. Correlation between pharmacokinetics and pharmacodynamics of tacrolimus in the treatment of pediatric renal transplant patients. Bol. Med. Hosp. Infant. Mex. [online]. 2013, vol.70, n.3, pp.209-215. ISSN 1665-1146.

Background. Tacrolimus is a widely used immunosuppressant in renal transplant patients. Drug monitoring is performed by measuring trough levels. Pharmacodynamic monitoring is used to evaluate the biological effect. The aim of the study was to determine the relationship between tacrolimus area-under concentration vs. time curve (AUC) and the gene expression of tumor necrosis factor alpha (TNF-α) in children with renal transplant. Methods. An experimental, cross-sectional study was performed in children with renal transplant at 3 months after transplant. An 8-h pharmacokinetic-pharmacodynamic profile was obtained. Gene expression of TNF-α and internal control of 18s rRNA was performed by real-time PCR. CYP3A5 genotype was obtained by direct sequencing. Results. Six patients were included with a median age of 14.5 years. A negative correlation was found between tacrolimus pharmacokinetics and TNF-α gene expression. There was a trend of low TNF-α with high tacrolimus blood levels. Conclusions. There is a negative correlation between tacrolimus concentration and TNF-α gene expression. TNF-α gene expression was not modified by CYP3A5 genotype.

Keywords : tacrolimus; pharmacokinetics; pharmacodynamics; TNF-α; renal transplant; immunosuppression.

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