ka0.7WilliamsA value of 0.7 gives a tmax of about 1 h, consistent with the literature
V23.5 * 29Williams3.5 L/kg * body wt
KeCln(2)/3.5WilliamsKeC = natural log of 2 divided by half-life
0.005bWilliamsaThis number was empirically derived to correspond to ∼10% conversion of a single dose of codeine to morphine, given the other parameters in the model, which is the widely quoted extent for normal adult individuals.
bAs described in the Williams article, children aged 5 typically have 25% of the conversion capability of adults.
V32.8 * 29KartKart et al summarized many studies of morphine in children.
KeMln(2)/2.0KartSee KeC.
  • The inputs provided into this 3-compartment model included Weight = 29 kg; dose = 12 mg at time 0, 4, 8, 11 hours; codeine concentration = 79 ng/mL at time 19 hours; and morphine concentration = 30 ng/mL at time 19 hours. A twofold variance around each value was used to account for variance in the population. f, rate of conversion of codeine to morphine in an intermediate metabolizer; ka, absorption rate constant from compartment 1 (the gut); KeC, codeine elimination rate (constant); KeM, morphine elimination rate (constant); V2, vol of distribution of codeine into compartment 2; V3, vol of distribution of morphine into compartment 3.