Table 3.
Base model population estimates for the pharmacokinetic parameters of R (+) (NONMEM Objective Function Value OFV −206.749) and S (−) (OFV −333.939) Ketorolac in 8 infants aged 2.5–6 months combined with previously studied dataset comprising 25 infants and toddlers (aged 6–18 months). The covariate model for S (−) ketorolac (OFV −337.764) is also reported.
Parameter Estimates | Between-Subject Variability |
|||
---|---|---|---|---|
Valuea (θ) | S.E.(%)b | |||
BSVc (ω) | S.E (%).b | |||
R (+) Ketorolac Base Model | ||||
CL (ml/min) | 7.91 | 9.4 | 0.244 | 29.1 |
V1 (ml) | 1110 | 9.0 | 0.304 | 23.4 |
Q (ml/min) | 6.74 | 14.8 | NE | NE |
V2 (ml) | 670 | 17.3 | 0.373 | 68.9 |
σ2 | ||||
Proportional | 0.0305 | 21.8 | ||
Additive | 0.00436 | 45.0 | ||
S (−) Ketorolac Base Model | ||||
CL (ml/min) | 39.5 | 13.0 | 0.462 | 33.3 |
V1 (ml) | 1930 | 15.2 | 0.471 | 23.6 |
Q (ml/min) | 95.1 | 3.1 | NE | NE |
V2 (ml) | 319 | 58.3 | 1.76 | 45.1 |
σ2 | 0.0176 | 59.7 | ||
S (−) Ketorolac Covariate Model | ||||
Intercept on CL (ml/min) | 40.3 | 10.3 | 0.380 | 30.0 |
Normalized slope on CL | 1.04 | 2.16 | ||
(1/month) | 2060 | 11.8 | 0.447 | 22.2 |
V1 (ml) | 94.2 | 3.96 | NE | NE |
Q (ml/min) | 205 | 54.6 | 2.71 | 39.1 |
V2 (ml) | 0.0179 | 59.2 | ||
σ2 |
Fixed-effect parameters: clearance (CL), central volume of distribution (V1), inter-compartmental clearance (Q) and peripheral volume of distribution (V2). Residual error parameters: variance of the exponential error model for R (+) ketorolac and variance of the additive error model for S (−) ketorolac. NE, not estimated.
Standard error expressed as percent coefficient of variation.
BSV, between-subject variability expressed in variance units (approximately coefficient of variation squared).