Conversion from Prograf to Advagraf in Adolescents with stable liver transplants: Comparative pharmacokinetics and 1‐year follow‐up

The recommended dose of Advagraf for conversion from Prograf is considered to be 1:1 on a milligram basis. However, the long‐term equivalence of Prograf and Advagraf has been questioned. The relative bioavailability of Advagraf and Prograf was evaluated in a single‐center, open‐label study of Prograf‐to‐Advagraf conversion in 20 patients, ranging in age from 12 to 18 years, who had a stable liver transplant and were receiving Prograf. After the supervised administration of Prograf for 7 days, the patients were converted to Advagraf. On days 7 and 14, serial blood samples were obtained for tacrolimus determinations. The pharmacokinetic parameters were calculated with a noncompartmental approach, and the relative bioavailability of both formulations was calculated according to standard statistical methods. Polymorphisms in cytochrome P450 3A5 (rs776746), adenosine triphosphate–binding cassette B1 (rs1045642), POR*28 (rs1057868), and POR (rs2868177) were determined with standard methods. The clinical and analytical data from a 1‐year follow‐up period were collected for all patients 30, 90, 180, and 360 days after conversion. The mean ratios for C max and AUC 0‐24 were 96.9 (90% confidence interval = 85.37‐110.19) and 100.1 (90% confidence interval = 90.8‐112.1), respectively. No relationship was found between the patients' genotypes and the pharmacokinetic tacrolimus values. During the follow‐up, biochemical parameters (aspartate aminotransferase, alanine aminotransferase, bilirubin, cystatin C, and creatinine) did not change significantly; 3 patients presented with relevant clinical events, but no event was considered to be related to tacrolimus. A decrease in tacrolimus blood levels and an increase in dose/level ratios were observed 3 and 6 months after conversion, but they returned to basal levels by month 12. In conclusion, conversion from Prograf to Advagraf with a 1:1 dose equivalence is appropriate as an initial guideline. Our 1‐year follow‐up showed a transient decrease in tacrolimus levels, so closer monitoring of tacrolimus levels may be required after conversion. Liver Transpl 19:1151–1158, 2013 . © 2013 AASLD.