TABLE 3.
Model evaluation for MPH.
| AUC (ng·h/ml) | Cmax (ng/ml) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Dose | N | Mean observed | Mean predicted | PE (%) | Mean observed | Mean predicted | PE (%) | ||
| d/dl-MPH | |||||||||
| Calibration Datasets | |||||||||
| (Midha et al., 2001) | 40 mg Ritalin | 24 | 59.1 | 90.8 | 53.7 | 11.7 | 16.9 | 45.1 | |
| (Midha et al., 2001) | 40 mg Ritalin (fed) | 24 | 68.1 | 103 | 51.2 | 14.3 | 15.6 | 9.1 | |
| (Patrick et al., 2007) | 0.3 mg/kg Ritalin | 20 | 82.9 | 54.5 | −34.3 | 15.3 | 8.5 | −44.4 | |
| (Spencer et al., 2006) | 40 mg Ritalin | 12 | 81.9b | 97.1 | 18.5 | 14.1 | 15.7 | 11.3 | |
| (Teo et al., 2004) | 20 mg Focalin | 15 | 121 | 96.1 | −20.5 | 23.7 | 18.1 | −23.7 | |
| (Teo et al., 2004) | 20 mg Focalin (fed) | 15 | 132 | 99.6 | −24.5 | 22.1 | 15.5 | −30.0 | |
| (Patrick et al., 2013) | 0.3 mg/kg Ritalin | 24 | 52.1 | 53.4 | 2.5 | 10.1 | 8.2 | −18.8 | |
| (Patrick et al., 2013) | 0.15 mg/kg Focalin | 24 | 53.7 | 53.4 | −0.6 | 10.7 | 8.2 | −23.4 | |
| (Parasrampuria et al., 2007) | 50 mg Ritalin | 49 | 106 | 125 | 17.9 | 21.1 | 24.0 | 13.7 | |
| (Parasrampuria et al., 2007) | 90 mg Ritalin | 49 | 195 | 226 | 15.9 | 38.8 | 43.2 | 11.3 | |
| Verification Datasets | |||||||||
| (Hysek et al., 2014) | 60 mg Ritalin | 15 | 175a | 172 | −1.9 | 30.4 | 32.4 | 6.6 | |
| (Abbas et al., 2016) | 40 mgc Ritalin | 29 | 132 | 202 | 52.6 | 15.6 | 22.9 | 46.8 | |
| (Adjei et al., 2014) | 25 mgd Ritalin | 24 | 282 | 188 | −33.3 | 29.1 | 18.0 | −38.1 | |
| (DeVane et al., 2000) | 10 mg Ritalin | 6 | 23.7a | 19.7 | −16.9 | 4 | 4.5 | 12.5 | |
| (Koehm et al., 2010) | 20 mg Ritalin | 9 | 35 | 43 | 22.9 | 7 | 7.1 | 1.4 | |
| (Meyer et al., 2000) | 20 mg Ritalin | 20 | 35.8 | 48.9 | 36.5 | 7.6 | 8.8 | 15.9 | |
| (Patrick et al., 1989) | 10 mge Ritalin | 18 | 42.0 | 45.3 | 7.8 | 6.4 | 4.8 | −25.3 | |
| (Spencer et al., 2012) | 40 mgf Ritalin | 26 | 179a | 185 | 3.3 | 25.4 | 22.6 | −10.8 | |
| (Stage et al., 2017) | 10 mg Ritalin | 16 | 21.4g | 23.2g | 18.7 | 5g | 3.9g | −19.2 | |
| (Wong et al., 1998) | 40 mg Ritalin | 21 | 93.6 | 90.1 | −3.7 | 17.8 | 16.4 | −7.9 | |
| Weighted PE (%) | 11.7 | -0.8 | |||||||
| l-MPH | |||||||||
| (Wong et al., 1998) | 40 mg Ritalin | 21 | 1.51 | 1.33 | −11.9 | 0.821 | 0.54 | −34.2 | |
| (Patrick et al., 2013) | 0.3 mg/kg Ritalin | 24 | 0.77 | 0.72 | −6.5 | 0.18 | 0.22 | 22.2 | |
| (Patrick et al., 2007) | 0.3 mg/kg Ritalin | 20 | 0.82a,b | 0.80 | −2.4 | 0.22b | 0.25 | 13.6 | |
| Weighted PE (%) | -7.0 | 1.3 | |||||||
PK parameters shown as arithmetic mean values unless otherwise noted.
a AUC0-last
b Obtained from a non-compartmental analysis of digitized population-level data.
c Two doses administered 6 hours apart.
d Three doses administered 4 hours apart.
e Two doses administered 5 hours apart.
f Two doses administered 4 hours apart.
g Values shown as median.