Low tacrolimus dose requirements in renal transplant recipients in the omani population: implications for pharmacogenetics?

Clinical observations suggested that the dose requirements for some immunosuppressive drugs might be lower in some Eastern populations. We performed a study of 50 among 162 patients who were converted from a cyclosporine-based immunosuppression regimen to one based on tacrolimus. The reasons for conversion were as follows: acute rejection (n = 23), hirsutism and gingival hypertrophy (n = 12), chronic allograft nephropathy (n = 4), hypertension (n = 3), and other reasons (n = 8). Target levels were 10-15 ng/mL for patients with acute rejection and 5-8 ng/mL for patients after the first year of transplantation. We measured 180 tacrolimus blood levels in 44 patients using the IMx Abbott system of mean weight 64.5 kg and mean daily dose of 4.89 +/- 2.56 mg with mean blood levels of 11.31 +/- 5.22 ng/mL. Thus, to achieve the above-mentioned levels the average dose was 0.076 mg/kg, which is lower than that generally recommended to achieve 5-8 ng/mL levels, namely, 0.15 mg/kg. In this study, we did not address the reasons for these findings. The possibilities include dietary factors influencing the absorption of tacrolimus, and genetic polymorphisms in the Omani population that affect drug levels through several possible pharmacogenetic/genomic mechanisms. We intend to perform such studies in the future.