Weight-based tacrolimus trough concentrations post liver transplant

Area of Science:

• Pharmacology
• Transplantation Medicine
• Clinical Pharmacy

Background:

• Tacrolimus is a critical immunosuppressant following liver transplantation.
• Obesity is a growing concern in liver transplant recipients, necessitating research into body size effects on drug therapy.
• Understanding tacrolimus pharmacokinetics in relation to body weight is essential for optimizing post-transplant outcomes.

Purpose of the Study:

• To determine if patient body weight influences tacrolimus trough plasma concentrations with standard mg/kg dosing.
• To compare the incidence of sub-therapeutic or supra-therapeutic tacrolimus levels between obese and non-obese liver transplant patients in the early post-transplant period.

Main Methods:

• Analysis of tacrolimus trough concentrations from a transplant database of 69 patients.
• Initial tacrolimus dosing at 0.1 mg/kg/day, adjusted to target trough concentrations.
• Evaluation of trough blood samples, phenotypic, and outcome variables.

Main Results:

• Tacrolimus trough concentrations were comparable between obese and non-obese groups across all sampling points (P > 0.05).
• A high percentage of patients, regardless of weight status, had concentrations outside the therapeutic range in the first week post-transplant (Obese: 85.7%, Non-obese: 79.5%).
• The proportion of concentrations outside the therapeutic range decreased over time but remained significant at 6 months.

Conclusions:

• Standard mg/kg dosing of tacrolimus appears to adequately account for body weight in terms of initial drug exposure post-liver transplant.
• Obese liver transplant recipients do not experience a disproportionately higher number of tacrolimus concentrations outside the therapeutic range compared to non-obese individuals.
• Close therapeutic drug monitoring is crucial for all liver transplant patients, irrespective of body size, particularly in the early post-transplant phase.