. 2017 Nov 7;84(1):97–111. doi: 10.1111/bcp.13400

Table 1b.

Overview of the population pharmacokinetic models used for the evaluation of drug–drug interactions of phenobarbital, phenytoin, topiramate, valproate and zonisamide

Model	Phenobarbital	Phenytoin	Topiramate	Valproate Adults	Valproate Children	Zonisamide
First author	Goto 20	Odani 21	Girgis 22	Blanco‐Serrano 23	Blanco‐Serrano 24	Okada 25
Population	Japanese	Japanese	NA (Caucasian presumably)	Spanish	Spanish	Japanese
Sample size (No. of patients)	79	116	1217	255	208	99
Sample size (No. of patients)	260	531	4640	770	534	282
Age (y)	0.8–44	1–37	2–85	14–95	0.1–14	1.36–39.24
Weight (kg)	8–80	42.4 ± 16.5	NA	4–74	27–100	10–117
Samples at	TDM	Peak/Trough	NA	TDM	TDM	4.3 ± 2.8 h after dose
Graphical representation
Parameters	K_a, V_c, CL	V_c, CL (V_max, K_m)	K_a, V_ss (V₁ + V₂), K₁₂, K₂₁, CL	K_a, V_c, CL	K_a, V_c, CL	K_a, V_c, CL
Between‐subject variability	V_c, CL	V_c, V_max, K_m	K_a, V_c, CL	CL	CL	CL
Covariate effects on CL	WT, PHT, VPA	WT, daily PHT dose, ZNS	Age, WT, Inducers (CBZ/PHB/PHT), VPA, NEMD, ZNS	WT, Dose, CBZ, PHT, PHB	WT, Dose, CBZ	WT, Dose, CYP2C19 genotype, CBZ, PHB, PHT
Covariate effects on V	‐	WT	WT	WT	WT	WT

CL, clearance; K_a, absorption rate constant; Km, Michaelis‐Menten constant; K₁₂/K₂₁, distribution rate constants from and to central and peripheral compartments, respectively; NA, not available; TDM, therapeutic drug monitoring; V, volume of distribution; V₁ / V_c, volume of distribution of the central compartment; V₂, volume of distribution of the peripheral compartment, V_max, maximum metabolic capacity; WT, weight