Comparison of three estimators for determining cyclosporine dosing in infants after liver transplantation

Abstract

Objective: To compare and analyze how allometrically- and linearly-scaled daily doses of cyclosporine could affect the therapeutic drug monitoring concentrations when applied to 8 infants with liver transplants.

Materials and methods: Eight infants who underwent liver transplantations were put on twice-daily oral cyclosporine immunosuppressive regimens. After starting therapy, the adjustments of individual daily doses were determined by using therapeutic monitoring of plasma cyclosporine levels by measuring trough concentrations (C₀) and concentrations at 2 hours after drug administration (C₂). These doses were analyzed and compared with the hypothetical doses estimated by allometric and linear scaling in order to compare which of the two methods would yield closer estimates to the actual doses applied.

Results: The median therapeutic drug monitoring (TDM)-based dose (n = 53) was 70.00 mg (10.9 mg/kg/day) (5.00 - 190.00 mg), whereas the median allometric (n = 53) and linear (n = 53) doses were 65.21 mg (10.11 mg/kg/day) (57.17 - 79.25 mg) and 35.63 mg (5.52 mg/kg/day) (29.89 - 46.20 mg), respectively. The median allometric dose was significantly different than the median linear dose (p < 0.0001), whereas there was no statistical difference between the median TDM-based dose and median allometric dose (p = 0.72).

Conclusions: The allometric approach, when used to estimate cyclosporine doses in this cohort of liver transplant infants, yielded closer estimates to actually applied daily doses in comparison to linear scaling. Allometric scaling could be employed in calculating starting doses for drugs that lack specific dosing recommendations for infants, in order to achieve therapeutic levels faster, lowering the need for constant monitoring and dose adjustment. .