TABLE 2

Estimated parameter values for the final PK model

ParametereValue90% CIaDescription
Fixed effects
    Ka(–)MQ (1/h)0.1570.023–0.303First-order absorption rate constant for (–)MQ
    Vcentral,(–)MQ/F (liters)b476132–801Apparent volume of distribution central compartment for (–)MQ
    Q(–)MQ/F (liters/h)85.712.8–120.5Intercompartmental clearance of (–)MQ
    Vperipheral,(–)MQ/F (liters)860657–1,173Apparent volume of distribution peripheral compartment for (–)MQ
    CL(–)MQ/F (liters/h)1.491.38–1.60Apparent clearance of (–)MQ
    Ka(+)MQ (1/h)0.2090.032–0.329First-order absorption rate constant for (+)MQ
    Vcentral,(+)MQ/F (liters)b814252–1,230Apparent volume of distribution central compartment for (+)MQ
    Q(+)MQ/F (liters/h)14122.2–182Intercompartmental clearance of (+)MQ
    Vperipheral,(+)MQ/F (liters)1,070808–1,492Apparent volume of distribution peripheral compartment for (+)MQ
    CL(+)MQ/F (liters/h)8.287.55–9.28Apparent clearance of (+)MQ
    Vcentral,CMQ/F (liters)47.87.6–62.0Apparent volume of distribution central compartment for CMQ
    QCMQ/F (liters/h)16.811.9–20.1Intercompartmental clearance of CMQ
    Vperipheral,CMQ/F (liters)968657–1,063Apparent volume of distribution peripheral compartment for CMQ
    CLCMQ/F (liters/h)1.120.78–2.58Apparent clearance of CMQ
    Emax3.380.54–5.07Maximum induction of synthesis rate
    EC50 (nmol/liter)2.45FIXcCMQ concn achieving half-maximum induction effect
    Kdeg (1/h)0.004530.00144–0.6433Elimination rate of metabolizing enzyme pool
    WTexponent1.330.42–2.48Effect of wt on V1,(–)MQ/F and V1,(+)MQ/F
    SPLIT1.051.01–1.16Effect of split dose on relative bioavailability
    CORD1FIXcRatio of drug concentration in cord blood to that in plasma
Random effects: interindividual variability
    IIV Vcentral,MQ (%CV)11980.3–189IIV on volume of distribution central compartment for (–)MQ and (+)MQ
    IIV CLMQ (%CV)34.633.7–47.3IIV on clearance of (–)MQ and (+)MQ
    IIV CLCMQ (%CV)42.739.4–55.6IIV on clearance of CMQ
Random effects: residual variabilityd
    PRV(–)MQ plasma (%)29.927.6–34.8Proportional residual error for (–)MQ in plasma
    ARV(–)MQ plasma (± nmol/liter)5313.4–69.9Additive residual error for (–)MQ in plasma
    PRV(+)MQ plasma (%)38.535.7–45.4Proportional residual error for (+)MQ in plasma
    ARV(+)MQ plasma (± nmol/liter)128.4–17.5Additive residual error for (+)MQ in plasma
    PRVCMQ plasma (%)24.821.5–35.6Proportional residual error for CMQ in plasma
    ARVCMQ plasma (± nmol/liter)638.6–94.8Additive residual error for CMQ in plasma
    PRV(–)MQ cord (%)3922.6–47.1Proportional residual error for (–)MQ in cord
    ARV(–)MQ cord (± nmol/liter)291.2–36.4Additive residual error for (–)MQ in cord
    PRV(+)MQ cord (%)18048.2–257Proportional residual error for (+)MQ in cord
    ARV(+)MQ cord (± nmol/liter)21.7–3.7Additive residual error for (+)MQ in cord
    PRVCMQ cord (%)40.237.6–55.9Proportional residual error for CMQ in cord
    ARVCMQ cord (± nmol/liter)10.1–5.8Additive residual error for CMQ in cord
  • a 90% CI, ninety percent bootstrap confidence interval based on 250 replicates.

  • b V1,(–),(+)MQ/F – individual = V1,(–),(+)MQ/F × (individual weight/55)WTexponent.

  • c Parameters were fixed to the respective value and were not estimated by the algorithm.

  • d PRV, proportional residual variability; ARV, additive residual variability.

  • e /F, over bioavailability.