Changes in CYP450 enzyme activity over time following liver transplantation

Aim This study was designed to evaluate CYP450 enzyme activity in liver transplant (OLTx) patients. Methods Thirty-nine stable OLTx patients (mean age 51 yrs) studied on 69 occasions were given an oral 5-drug Pittsburgh cocktail to assess CYPs 1A2, 2C19, 2D6, 2E1 and 3A. Concentrations of drugs/metabolites were determined by HPLC for phenotype analysis. Seven elderly and 14 young healthy subjects (mean ages 77 and 21 yrs) were studied as controls. Results Within 30 days postoperatively, 2E1 activity was higher compared to young controls (mean±SD 5.8±4.6 vs 0.8±0.3, p<0.01), but subsequently returned to control values. 2C19 capacity was markedly lower compared to elderly controls (48.2±30.7 vs 104.8±59.9, p<0.01), and 3A activity was also lower. After 30 days postoperatively, the 2D6 capacity was lower compared to elderly controls (0.34±0.24 vs 0.66±0.13, p<0.01). There was no change in CYP1A2. Conclusions Selective regulation of CYPs included an early increase in activity of 2E1, decreased activity of 2C19 and 3A, a late decrease in 2D6, but no change in activity of CYP1A2. Drugs that are substrates of these enzymes may require dosage adjustment accordingly. Clinical Pharmacology & Therapeutics (2005) 77, P34–P34; doi: 10.1016/j.clpt.2004.12.024