Pharmacokinetic and prognostic significance of intestinal MDR1 expression in recipients of living‐donor liver transplantation

• DOI: 10.1067/mcp.2001.115142
• Publication Date: 2002-07-25T04:21:43Z
• Authors: Tohru Hashida; Satohiro Masuda; Shinji Uemoto; Hideyuki Saito; Koichi Tanaka; Ken‐ichi Inui
• Keywords: Trough level; Regimen; Therapeutic Drug Monitoring

Living-donor liver transplantation (LDLT) and subsequent immunosuppressive therapy with tacrolimus have been cornerstones in the recovery of patients from end-stage failure, but there has no critical dosage regimen for therapy, especially initial dosage. In this study, we examined whether absorptive barriers, multidrug resistance protein (MDR1), or cytochrome P450 IIIA4 (CYP3A4) are important pharmacokinetic factors prognostic indicators LDLT outcome.We used competitive polymerase chain reaction to evaluate messenger ribonucleic acid (mRNA) expression levels MDRL And Cyp3A4 mucosal cells upper jejunum a part Rroux-en- Y limb biliary reconstruction during recipients (n = 48). The was started at an oral dose 0.075 mg/kg every 12 hours adjusted on basis its whole-blood trough level by use semiautomated microparticle enzyme immunoassay.The mRNA MDR1 (r -0.776), not CYP3A4 -0.094), inversely related concentration/dose ratio tacrolimus. High MDR1, CYP3A4, were strongly associated reductions survival rates after Kaplan-Meier method log-rank statistics (P =.020 P =.135, respectively). With Cox regression procedure, high (relative risk, 12.99; 95% confidence interval, 1.64-103.23), 0.93; 0.87-1.00) appeared be significant indicator poor survival.Intestinal is only good probe which predict interindividual variation pharmacokinetics also powerful outcome LDLT.