Table 2.
Parameter Estimates
| Parameters | Estimate | RSE% |
|---|---|---|
| Parent PK Model | ||
| Ka (hr−1) | 0.416 (FIX) | |
| CL (L/hr) | 203 | 12 |
| V2 (L) | 142 | 142 |
| Q (L/hr) | 1010 | 96 |
| V3 (L) | 6350 | 61 |
| KM (day) | 2.18 | 29 |
| SLP | 5 (FIX) | |
| EMAX | 0.477 (FIX) | |
| TF | 0.104 | 32 |
| KM1 (day) | 4.79 | 24 |
| SLP1 | 5 (FIX) | |
| BASE1 | 0.0268 (FIX) | |
| Additive Error | 0 | |
| Proportional Error | 0.58 | 6 |
| CL-ISV (%) | 49.9 | 17 |
| V2-ISV (%) | 363 | 53 |
| V3-ISV (%) | 74.1 | 12 |
| Metabolite PK Model | ||
| Fraction | 50% (FIX) | |
| V4 (L) | 2930 | 30 |
| CL40 (L/hr) | 187 | 12 |
| KM2 (day) | 6.99 | 17 |
| SLP2 | 5 (FIX) | |
| BASE2 | 0.479 | 23 |
| Additive Error | 0.010 | 48 |
| Proportional Error | 0.28 | 10 |
| V4-ISV (%) | 74.8 | 28 |
| CL40-ISV (%) | 50.9 | 13 |
| NAS PD Model | ||
| KNAS | 0.0724 | 32 |
| E2MAX | 1.25 | 58 |
| HILL | 1.36 | 55 |
| EC50 (ng/mL) | 0.509 | 78 |
| NASKM (day) | 0.0818 | 191 |
| NASHILL | 0.454 | 21 |
| NASMAX | 5.11 | 69 |
| DRUGK (1/day) | 0.56 | 28 |
| Additive Error | 2.32 | 3 |
| KNAS-ISV (%) | 0.0579 | 56 |
| NASKM-ISV (%) | 0.333 | 41 |
Ka = absorption rate constant, CL = clearance, V2 = volume of distribution of buprenorphine in the central compartment, V3 = volume of distribution of buprenorphine in the peripheral compartment, Q = intercompartmental clearance, KM/KM1= ontogeny maturation rate constants, SLP/SLP1/HILL = hill constant in sigmoidal model, EMAX = maximum hepatic function, TF = exponential growth factor, BASE1/2 = proportion of hepatic function at birth, ISV = inter-subject variability, V4 = apparent volume of distribution of norbuprenorphine, CL40 = apparent clearance of norbuprenorphine, KNAS = rate constant of NAS chnage, E2MAX = maximal pharmacodynamic effect of buprenorphine, EC50 = concentration producing half-maximal pharmacodynamics effect, NASKM, NASMAX = constant representing maximum rate of NAS worsening, NASHILL = constant describing slope of NAS course, DRUGK = rate constant representing the clearance of opioid transferred in utero, L=liters, hr=hours