Table 2.

Final model pharmacokinetic parameter estimates and SIR results

Parameter	Phenobarbital		Midazolam		OHMa		HMGa
	estimate	SIRb 95% CI	estimate	SIRc 95% CI	estimate	SIRc 95% CI	estimate	SIRc 95% CI
Cl,L/hd	10.3	8.38–12.1	0.353	0.286–0.441	3.39	2.75–4.01	0.191	0.170–0.214
V, Ld	3.60	3.43–3.79	5.42	4.49–6.81	4.18 (fixed)	NA (fixed)	1.06	0.834–1.27
TEMPon Cl, %/°C	NA	NA	NA	NA	8.58	5.63–11.5	NA	NA
PBonCl, fold	NA	NA	2.33	1.88–2.92	NA	NA	NA	NA
Interindividual variability
Cl, variance (rsd)	0.287 (54%)	0.148–0.498	0.628 (79.2%)	0.479–0.847	0.633 (79.6%)	0.472–0.818	0.241 (49.1%)	0.174–0.338
V, variance (rsd)	0.0442 (36%)	0.0305–0.0659	0.934 (96.6%)	0.583–1.27	NA (fixed)	NA (fixed)	0.837 (91.5%)	0.353–1.33
Residual variability
Additional, mg/L (rse)	2.52 (31%)	2.32–2.79	0.01(fixed)	NA (fixed)	0.01 (fixed)	NA (fixed)	0.01 (fixed)	NA (fixed)
Proportional, variance (rsd)	NA	NA	0.126 (35.5%)	0.107–0.164	0.0857 (29.3%)	0.0683–0.119	0.0871 (29.5%)	0.0729–0.112

Covarianceinterindividual variability onCl			Midazolam/OHM		Midazolam/HMG		OHM/HMG
			estimate	SIRc 95% CI	estimate	SIRc 95% CI	estimate	SIRc 95% CI
Covariance (correlation coefficient)			0.500 (79.0%)	0.378–0.652	0.214 (55.0%)	0.133–0.310	0.233 (60.0%)	0.147–0.327

Cl, clearance; V, volume of distribution; TEMP, body temperature; PB, phenobarbital co-medication; OHM, 1-hydroxymidazolam; HMG, hydoxymidazolam glucuronide; SIR, sampling importance resampling; NA, not applicable; rsd, relative standard deviation; rse, relative standard error.

^aAll metabolite estimates are relative to formation fraction FOHM and FHMG, resp.

^bFive iterations; no. of samples 4,000, 4,000, 4,000, 4,000, 4,000; no. of resamples 1,000, 1,000, 1,000, 1,000, 2,000;

^cSix iterations, no. of samples 4,000, 4,000, 4,000, 4,000, 4,000, 4,000; no. of resamples 1,000, 1,000, 1,000, 1,000, 1,000, 1,000;

^dEstimates for neonate with a birth weight of 3.5 kg.