Table 1.

PK Profiles for Simulation Study.

Category	Description		Vocabulary (Abbreviation)
Simulation Scenario
PK profile	Two PK profiles represent drugs with fast- vs. slow-elimination.		Fast-Elimination (FEL) Slow-Elimination (SEL)
	FEL Parameters ka (h−1): 1 CL (L/h): 0.2 V (L): 2 ke (h−1): 0.1 D (mg): 300	SEL Parameters ka (h−1): 3.09 CL (L/h): 22.7 V (L): 1090 ke (h−1): 0.02 D (mg): 5
Variability	Each PK profile takes on varying levels of between- and within-subject variability: two sets of parameters, low- vs. high-variability.		Low-Variability (LV) High-Variability (HV)
	LV Parameters ωCL (%CV): 5 ωV (%CV): 5 σprop (%CV): 5 σadd,FEL (ng/ml): 1 σadd,SEL (ng/ml): 0.1	HV Parameters ωCL (%CV): 30 ωV (%CV): 30 σprop (%CV): 30 σadd,FEL (ng/ml): 5 σadd,SEL (ng/ml): 0.5
Design of concentration measurements	Concentration measurements can occur at different times across the concentration-time profile. Simulated datasets follow one of three designs, which define when observations are taken following dosing: Full Observation: collect blood concentrations at 1, 3, 5, 7, 9, and 11 hours after dosing. 3 hour + trough: collect blood concentrations at 3 and 11 hours (trough) after dosing. Trough: collect blood concentrations 11 hours after dosing.		Full observation (FO) 3 hour + trough (3T) Trough (TR)
Evaluation
Dose timing	Simulated datasets were built with accurate true dosing vs. inaccurate assumed dosing.		True dosing (TD) Assumed dosing (AD)
ka assumption	The PK model was fit with fixed absorption rate, ka, at one of three values True ka: the same fixed ka used to simulate the population. Low ka: the true ka divided by 10. High ka: the true ka multiplied by 10.		True ka Low ka High ka

Nomenclature, descriptions, and true underlying parameters are defined to describe two PK profiles with slow- (SEL) and fast-elimination (FEL). A total of four profiles, two scenarios of variability (low, high) for each of SEL and FEL, are created by taking either the low or high values for ωs and σs. The k_e, CL, V, and k_a represent population PK parameters for elimination rate constant, clearance, volume of distribution, and absorption rate constant, respectively. The D is the twice-daily dose. The ω _CL and ω _V are the between-subject variance components for clearance and volume of distribution, presented as %CV. The σ_prop and σ_add represent the proportional and additive residual errors in the combined residual error model, presented as %CV and standard deviation, respectively.