Pharmacokinetics of tacrolimus according to body composition in recipients of kidney transplants

Abstract

BackgroundCurrently, the dosage of tacrolimus used after transplantation is based on the patient's body weight. However, there is a low correlation between body weight and body composition in kidney transplant recipients. In this study, we evaluate the pharmacokinetics of tacrolimus according to body composition in 18 Korean kidney transplant recipients with stable graft function.MethodsBody composition parameters were calculated using bioelectrical impedance analysis. Pharmacokinetic profiles were determined 0, 1, 2, 3, and 4 hours after treatment with tacrolimus and were compared between high- and low-level median body composition groups. The values of C0, C1, C2, C3, and C4 were used in determining an abbreviated area under the curve (AUC) for tacrolimus.ResultsThe mean body mass index (BMI) and body composition values were as follows: BMI, 24.3 kg/m2; lean mass, 49.8 kg; and fat mass, 17.4 kg. There were no statistical differences in pharmacokinetic profiles between groups with different BMIs. However, the C0 and C4 in the high-fat group were significantly elevated compared with those of the low-fat group (P=0.024 and 0.031, respectively). Furthermore, the C0, C2, C3, and C4 and the AUC were significantly different between the two lean mass groups (P=0.007, 0.038, 0.047, 0.015, and 0.015, respectively). Other variables, such as waist circumference and arm muscle circumference, did not differentiate between the pharmacokinetic profiles of tacrolimus.ConclusionTaken together, these data suggest that tacrolimus dose monitoring based on body composition may provide adequate dosage leading to favorable long-term outcomes.

Which Kidney Transplant Recipients Can Benefit from the Initial Tacrolimus Dose Reduction?

“…BMI, which generally increases with age, was shown to be independently related to increased Tc first level, when its value exceeded 24.6 kg/m 2 . It is probably partly due to the altered body fat mass in those patients, as it was shown that Tc dose monitoring based on bioimpedance-derived body composition may provide more adequate dosage that based on BMI [ 19 ]. Of note, in our study, the highest frequency of subjects with first supratherapeutic Tc blood level was observed in the subgroup where both age and BMI exceeded the cut-off values.…”

Weight‐based tacrolimus trough concentrations post liver transplant

“…for those with end‐stage liver disease due to ascites and sarcopenia). Han et al . reported in their kidney transplant study there were no statistical differences in pharmacokinetic profiles between groups with different BMI.…”

“…for those with end-stage liver disease due to ascites and sarcopenia). Han et al 18 reported in their kidney transplant study there were no statistical differences in pharmacokinetic profiles between groups with different BMI. However, significant difference in pharmacokinetics was observed between groups once specific body composition values estimated by bioelectrical impedance analysis (e.g.…”

Immunosuppressive drugs – diagnostic problems

“…Powodem występujących różnic mogą być takie czynniki jak: wiek, płeć pacjenta, oraz skład masy ciała, głównie procentowa zawartość tkanki tłuszczowej. Doniesienia naukowe z ostatniego okresu sugerują, że w przypadku dobierania odpowiedniego dawkowania terapeutycznego leków immunosupresyjnych powinno się brać pod uwagę, poza masą ciała pacjenta, również zawartość tkanki mięśniowej oraz tłuszczowej [22]. Współistnienie innych schorzeń, narząd przeszczepiony (nerka, wątroba, serce, płuca) oraz czas, jaki upłyną od zabiegu również w znaczącym stopniu wpływają na przyswajanie leku.…”