Comparison of tacrolimus levels obtained with twice-daily administration formulation (Prograf®) and with once-daily formulation (Advagraf®)

Background: To compare tacrolimus levels before and after change from conventional formulation (Prograf[sup]®)[/sup] to extend-release formulation (Advagraf[sup]®[/sup]).
Material/Methods: 100% of transplanted patients were treated with Prograf[sup]® [/sup]and change to Advagraf[sup]®[/sup] during January-May/2008. Data that was taken into account was: sex, age, type and date of transplantation (computer application Gestión Documental®), pharmacokinetic data (computer program Openlab[sup]®)[/sup]. C[sub]min[/sub] determinations by whole-blood enzyme immunoassay on IM[sub]X [/sub]analyzer (Abbott). Concentrations comparison was done by the Wilcoxon's test.
Results: There were 31patients (20 males), of an average age of 53.8±14.4 years, who were transplanted between August/1999-March/2008 (22/kidney, 6/liver, 2/lung). Before the change, Prograf[sup]®'[/sup]s average dose was 4.53±3.3 mg/day and average C[sub]min[/sub] =8.597±4.99 ng/mL. In 13 patients, with a C[sub]min-Prograf®[/sub] =7.438 ng/mL, clinicians kept the same dose when they change to new formulation, obtaining a [sub]Cmin-Advagraf®[/sub] =5.054±1.42 ng/mL; it suppose a decrease of 30,68% (p=0.001). In the rest of patients the dose does not remain during conversion: in 10 patients, with a Cmin Prograf® =6.09±2.59 ng/mL, they increased dose and a C[sub]min-Advagraf®[/sub] = 5.92±2.88 ng/mL was reached, and in 8 patients, with a C[sub]min Prograf®[/sub] =13.61±7.19 ng/mL, they diminished dose and a C[sub]min-Advagraf®[/sub] =6.56±3.47 ng/mL was obtained. C[sub]min-Advagraf®[/sub] were minor than C[sub]min-Prograf®[/sub] in all cases.
Conclusions: Clinicians do 1:1 dosage conversion, because the same behavior is expected for both formulations. They only change dose to try to modify previous concentrations. By blood levels monitoring, we observed that, in all cases, concentrations obtained with Advagraf[sup]®[/sup] were minor than with Prograf[sup]®[/sup]. This decrease, notably superior to what it is described in bibliography, presents a clinical relevancy which does necessary a confirmation by the AUC profiles comparison for both formulations.

Keywords: Barrett’s Oesophagus, Columnar mucosa, Cytocheratin 7, p53, CDX2 , Tacrolimus, Columnar mucosa