TABLE 1.

Parameters used to simulate digoxin CL_R

Reduction in filtration and secretion was performed to represent changes in renal impairment. Simulated population representative of the “healthy volunteers” population had an age, weight, and body surface area of 20 years, 81 kg, and 1.98 m², respectively. Serum creatinine (input parameter of model) was calculated for each scenario using the Cockcroft-Gault equation (Cockcroft and Gault, 1976), based on the target GFR and the age, weight, and body surface area of the population representative.

GFR	Serum Creatinine Concentration	OATP4C1 Abundance	PTCPGK
ml/min/1.73 m2	µmol/l		million PTC/g kidney
136.4a	76.5	1	60
140	74.5	1.03	61.6
120	86.9	0.88	52.8
100	104.3	0.73	44.0
80	130.4	0.59	35.2
60	173.9	0.44	26.4
40	260.8	0.29	17.6
20	521.7	0.15	8.8
15	695.6	0.11	6.6

^aRelative change in GFR for each scenario was calculated using the value of 136.4 ml/ min/m² as baseline and applied to the OATP4C1 abundance or PTCPGK parameter.