Intravenous Administration of Tacrolimus Stabilizes Control of Blood Concentration Regardless of CYP3A5 Polymorphism in Living Donor Liver Transplantation: Comparison of Intravenous Infusion and Oral Administration in Early Postoperative Period.

Background: We compared achievement rate of sufficient tacrolimus blood concentration in the early postoperative period and incidence of acute cellular rejection within 1 month after living donor liver transplantation (LDLT) between tacrolimus intravenous (IV) and oral administration groups.
Methods: From October 2005 to November 2016, 61 LDLT patients administered tacrolimus, who could be genotyped for CYP3A5*3 and *1, were chosen from the electronic record database. The patients were then divided into the 2 groups (an IV group [n = 38] and an oral group [n = 23]). We defined patients with 1*1 or *1*3 as expressors and those with *3*3 as nonexpressors. Sufficient trough level tacrolimus blood concentration on postoperative day (POD) 3 was defined as 10-20 ng/mL.
Results: Comparable concentrations were seen between the 2 groups, with mean blood concentration 13.7 ± 8.5 ng/mL in the oral group and 15.2 ± 4.3 ng/mL in the IV group. Achievement rate of sufficient tacrolimus concentration on POD 3 was significantly higher in the IV group than in oral group: 97% (37 of 38) vs 65% (15 of 23), respectively (P = .001). When we focused on achievement rate in the oral group according to CYP3A5 polymorphism, the frequency of expressors (17%) was significantly lower than that of nonexpressors (82%) (P = .016). However, in the IV group this negative influence was totally eliminated, resulting in high achievement rates regardless of CYP3A5 polymorphism. In terms of incidence of acute cellular rejection, there was no significant difference between the 2 groups (IV 32% vs oral 17%, P = .250).
Conclusion: IV administration of tacrolimus allowed us to obtain more stable control of blood concentration regardless of CYP3A5 genotype.
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