A Simple Novel Technique to Estimate Tacrolimus Dosages During the Early Post Kidney Transplantation Period

•For Asian kidney transplant recipients, the tacrolimus dose is highly variable because of the different genotypes of CYP3A5 in this population.•Individualization of the initial tacrolimus dose according to CYP3A5 genotypes has been recommended, particularly in Asian kidney transplant recipients.•We demonstrated that the 12-hour level after the first dose (C12-0) has strong correlation with early postoperative tacrolimus dose.•The C12-0 is an alternative technique for estimating the dose of tacrolimus.

BackgroundTacrolimus pharmacokinetics prediction by CYP3A5 genotyping is not available in many Asian resource-limited settings. Therefore, an alternative technique is needed to estimate the dose of tacrolimus perioperatively. The 12-hour level after the first dose (C12-0) is an alternative technique for estimating the dose of tacrolimus. This simple and inexpensive calculation technique can be used by any transplantation center.MethodsA prospective study on a cohort of 57 incident post-kidney transplant recipients was conducted. The whole-blood tacrolimus trough level (C12-0) was measured at 12 hours after the first dose (0.1 mg/kg) of orally administered tacrolimus during transplantation. Concomitant medications with CYP3A5 inhibitors/inducers were not allowed. Genotyping for CYP3A5 expression was carried out by reverse transcription polymerase chain reaction. The dosages and trough levels of tacrolimus at postoperative day 7 and postoperative months 1 to 3 were measured and analyzed for the dose requirements for therapeutic levels (mg/kg/d).ResultsThe doses of tacrolimus were widely diverse, ranging from 0.049 to 0.260 mg/kg/d and 0.031 to 0.298 mg/kg/d at day 7 and months 1 to 3, respectively. There were 9, 28, and 20 patients (15.8%, 49.1%, and 35.1%) with CYP3A5 *1/*1, *1/*3, and *3/*3, respectively. The CYP3A5 genotypes were significantly correlated with the target tacrolimus dose at day 7 (r2 = 0.307) and the stable dose at months 1 to 3 (r2 = 0.337). The C12-0 level also was significantly correlated with the dose of tacrolimus at day 7 (r2 = 0.546) and the stable dose at months 1 to 3 (r2 = 0.406).ConclusionsThere were strong correlations between the C12-0 level and the tacrolimus doses during the perioperative period at day 7 and the stable period at 1 to 3 months. Countries with limited resources for genotype testing can use the C12-0 level as an alternative to estimate the tacrolimus dose.