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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

We have investigated the importance of cytochrome P-450IIIA enzyme activity in influencing dosage of the immunosuppressive drugs FK 506 and cyclosporine after liver transplantation. Cytochrome P-450IIIA enzyme activity in vivo 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 micrograms/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-450IIIA activity alpha 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-450IIIA activity provided no comparable increase in correlation for FK 506 or cyclosporine.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

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