. 2012 Jul 6;39(4):393–414. doi: 10.1007/s10928-012-9258-0

Table 3.

Model structure and covariate options for the stepwise and single-objective, hybrid genetic algorithm model building approaches

Compound	NONMEM model structures tested^a,b	First-order (FO) or first-order conditional (FOCE) estimation	Covariates analyzed^c
Citalopram, IV	ADVAN3, TRANS4	FOCE with interaction	Continuous: age, body-mass index, fat mass, fat-free mass, weight
Citalopram, IV	ADVAN3, TRANS4	FOCE with interaction	Discrete: sex
DMAG, IV	ADVAN3, TRANS4	FOCE with interaction	Continuous: age, albumin, alanine aminotransferase, aspartate transaminase, bilirubin, blood urea nitrogen, body surface area, creatinine, weight
	ADVAN11, TRANS4
	(And possible inter-occasion variability on clearance, central volume, and first inter-compartment clearance)
			Discrete: sex
Escitalopram, oral [21]	ADVAN2, TRANS2	FOCE with interaction	Continuous: age, body-mass index, weight
Escitalopram, oral [21]	ADVAN4, TRANS4	FOCE with interaction	Discrete: clinical site, CYP2C19 genotype, race, sex
Olanzapine, oral [14]	ADVAN2, TRANS2	FOCE with interaction	Continuous: age
Olanzapine, oral [14]	ADVAN4, TRANS4	FOCE with interaction	Discrete: race, sex, smoking status
Perphenazine, oral [15]	ADVAN2, TRANS2	FOCE with interaction	Continuous: age, number of cigarettes per day, weight
	ADVAN4, TRANS4		Continuous: age, number of cigarettes per day, weight
	ADVAN4, TRANS4		Discrete: race, sex, smoking status, concomitant medication use
Risperidone, oral [16]	ADVAN2, TRANS2	FO	Continuous: age, weight
	ADVAN4, TRANS4		Discrete: race, sex, smoking status, concomitant medication use
	(And 1, 2, or 3 clearance subpopulations)
Ziprasidone, oral [17]	ADVAN2, TRANS2	FOCE with interaction	Continuous: age, height, number of cigarettes per day, weight
Ziprasidone, oral [17]	ADVAN2, TRANS2	FOCE with interaction	Discrete: race, sex, smoking status, concomitant medication use

^aADVAN2 is a one-compartment linear model with first order absorption, ADVAN3 is a two compartment linear model; ADVAN4 is a two compartment linear model with first order absorption; and ADVAN11 is a three compartment linear model

^bTRANS2 with ADVAN2 specifies model options for clearance (CL) and volume of distribution (V); TRANS4 with ADVAN3 or ADVAN4 specifies model options for CL, central volume (V1), inter-compartment clearance (Q), and peripheral volume (V2); and TRANS4 with ADVAN11 specifies model options for CL, V1, first inter-compartment clearance (Q1), V2, second inter-compartment clearance (Q2), and third compartment volume (V3)