Importance of cytochrome P-450IIIA activity in determining dosage and blood levels of FK 506 and cyclosporine in liver transplant recipients

✍ Scribed by Yilmaz Cakaloglu; J. Michael Tredger; John Devlin; Roger Williams

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 727 KB
• Volume: 20
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840200207

✦ Synopsis

We have investigated the importance of cytochrome P-45OIIIA enzyme activity in influencing dosage of the immunosuppressive drugs FK 506 and cyclosporine after liver transplantation. Cytochrome P-45OIIIA enzyme activity in uiuo was measured 1 yr postoperatively in 37 stable orthotopic liver graft recipients (21 receiving FK 506 and 16 given cyclosporine) by the erythromycin breath test and the production of monoethylglycinexylidide from lignocaine. A strong correlation existed between FK 506 dose and erythromycin breath test results (r = 0.583, p < 0.007), but no corresponding relationship with monoethylglycinexylidide production was observed. The FK 506 dose (14 to 196 pg.kg/day) also correlated closely with circulating predose levels of the drug in both plasma and blood (r = 0.538 and 0.731, p = 0.015 and <0.001, respectively). Although no correlation existed between cyclosporine dose (0.254 to 0.494 mg/kg/day) and trough blood levels, a relationship was demonstrated when erythromycin breath test results were included in the derived equation: Drug dose/cytochrome P-4SOIIIA activity a drug level (p = 0.011 vs. 0.175 without erythromycin breath test). A corresponding enhancement was demonstrated with erythromycin breath test results to relate FK 506 dose and plasma levels (p = 0.006 versus 0.015 without erythromycin breath test results), although breath test results and FK 506 levels were highly discordant (p > 0.8). The use of monoethylglycinexylidide test results as an alternative measure of cytochrome P-45OIIIA activity provided no comparable increase in correlation for FK 506 or cyclosporine. Dissimilar dependencies on blood flow and gender may underlie the contrasting predictive value of the monoethylglycinexylidide and erythromycin breath test results, but the latter may be valuable in predicting FK 506 dosage in organ graft