Table 2.

PK/PD model parameters for simvastatin

ADAPT parameter	Value	Corresponding parameter in Kim et al. [13]
PK component
K 21 (h−1)	2.76	K a
V 1 (L)	8980	V 2
K 10 (h−1)a	0.136	Calculated from CL2/V 2 (see below)
K 14 (h−1)a	0.058	Calculated from CL2/V 2 (see below)
V 4 (L)	1190	V 3
K 40 (h−1)b	0.322	Calculated from CL3/V 3 (see below)
Tau (h)	0.212	Lag
PD component
k in (mg/dL·h)	1.14	k in
E max	0.489	E max
EC50 (ng/mL)	66.97	–c
k out (mg/dL·h)/(mg/dL)	0.0114	k in/baseline LDL-C

The following model parameters were set to zero: V ₃, K ₁₃, K ₃₁, V ₅, K ₄₅, and K ₅₄

For the ADAPT parameters, single-digit subscripts correspond to the compartment numbers in the models. Two-digit subscripts indicate flux between numbered compartments

CL clearance, EC ₅₀ concentration producing half-maximal inhibition, E _max maximum inhibitory effect, K CL/V, m metabolite, p parent compound, PD pharmacodynamic, PK pharmacokinetic, Q intercompartmental clearance, V volume

^aCalculated from CL₂ and V ₂ in Kim et al. [13]. K ₁₀ = K ₁ × 0.7, K ₁₄ = K ₁ × 0.3. K ₁ = CL₂/V ₂ = 1740/8980 = 0.194 h⁻¹

^bCalculated from CL₃ and V ₃ in Kim et al. [13]. K ₄₀ = CL₃/V ₃ = 383/1190 = 0.322 h⁻¹

^cEC₅₀ values were obtained from Dansette et al. [17]