Drugs | Parameters Obtained by Model Fitting | ||||||
---|---|---|---|---|---|---|---|
K1 | k2 | k3 | K4 | k5 | Vp | k6 | |
ml/min/g cotyledon | min−1 | ml/min/g cotyledon | min−1 | ml/g cotyledon | min−1 | ||
Paroxetine | |||||||
Estimate | 3.25 | 0.0717 | 0.0779 | 9.67 | 0.00490 | NA | 0.0241 |
(S.D.) | (0.42) | (0.0217) | (0.0572) | (6.90) | (0.01442) | NA | (0.0695) |
Antipyrine | |||||||
Estimate | 0.259 | 0.353 | NA | NA | NA | 0.739 | NA |
(S.D.) | (0.016) | (0.044) | NA | NA | NA | (0.080) | NA |
Drugs | Parameters from the Literature or Derived from Our Data | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
fu | K1′ | fp,m | K1′′ | K1′/k2 | K1′′/k2 | K4′ | fp,f | K4′′ | K4′/k3 | K4′′/k3 | |
ml/min/g cotyledon | ml/min/g cotyledon | ml/g cotyledon | ml/min/g cotyledon | ml/min/g cotyledon | ml/g cotyledon | ||||||
Paroxetine | 0.263 | 12.4 | 0.050a | 0.618 | 172 | 8.61 | 36.8 | 0.050a | 1.84 | 472 | 23.6 |
Antipyrine | 0.926 | 0.280 | 0.884b | 0.247 | 0.792 | 0.700 | NA | 0.869b | NA | NA | NA |
fp,f, unbound fraction in human fetal plasma; fp,m, unbound fraction in human maternal plasma; fu, unbound fraction in perfusate; K1, K′1, K′′1, K4, K′4, K′′4, influx clearances into placental tissue; k2, k3, k5, k6, transfer rate constants; NA, not applicable; Vp, distribution volume of the placental compartment.
↵a The values in fetal and maternal plasma are not available, so the unbound fraction in healthy subjects was used.
↵b Ohkawa et al., 2001.