Table 3

Comparison of anidulafungin parameter estimates from population PK model at two stages (original data versus final data, FOCEI method)a

ParameterModeling approachTypical value (% RSEb)Interpatient % CV (% RSEb)
Original dataFinal dataOriginal dataFinal data
CL (liters/h)CL = θ1 + (wt − Mwt) × θ5 + gender × θ6 + study × θ728.0 (17.6)27.2 (16.2)
θ10.768 (3.80)0.777 (3.31)
θ50.00417 (26.9)0.00461 (21.6)
θ60.166 (25.4)0.183 (20.9)
θ70.278 (20.8)0.256 (20.7)
V1 (liters)V1 = θ2 × wtNSNS
θ20.215 (20.3)0.170 (24.0)
Q (liters/h)Q = θ3NSNS
θ320.3 (16.7)21.6 (10.5)
V2 (liters)V2 = θ4NSNS
θ419.6 (15.1)23.5 (11.0)
Vss (liters)33.4c34.6c14.3d10.0d
t1/2 (h)25.6c26.5c29.1d27.3d
Residual error parameter
σ21prop (%)24.0 (9.69)24.0 (9.79)NANA
• a Abbreviations: FOCEI, first-order conditional estimation with interaction; CL, clearance; V1, central volume of distribution; Q, intercompartmental clearance; V2, peripheral volume of distribution; Vss, volume of distribution at steady state; t1/2, terminal-phase half-life; σ21prop, proportional component of the residual error model; NS, not supported in model; NA, not applicable; wt, weight (kg); Mwt, 60 kg; gender, 1 for males and 0 for females; study, 1 for study 2 (ICC study) and 0 for all other studies.

• b % RSE, percent relative standard error of the estimate = SE/parameter estimate × 100 (for variability terms, this is the % RSE of the variance estimate). For original data, n = 225; for final data, n = 262.

• c Calculated from individual parameter values.

• d Calculated as (standard deviation/mean) × 100.