Definition | Abbreviation | Unit | Estimate^{a} | ||
---|---|---|---|---|---|

Population mean | Between-subject variability | Between-occasion variability | |||

Apparent maximum clearance without autoinhibition | CL/F_{70kg} | liters/h | 1.28^{b} | 33.4% | |

Distribution clearance between the central and peripheral compartments | CLd/F_{70kg} | liters/h | 0.714^{b} | 56.0% | |

Vol of central compartment | V1/F_{70kg} | liters | 12.3^{b} | 14.7% | |

Vol of peripheral compartment | V2/F_{70kg} | liters | 6.96^{b} | 46.6% | |

Vol of distribution at steady state | V_{ss}/F_{70kg} | liters | 19.2^{b,c} | ||

Concn causing half-maximal autoinhibition of clearance | IC_{50} | mg/liter | 46.3 | 36.5% | |

Maximum extent of autoinhibition | I_{max} | 0.710^{c} | 0.530–0.821^{d} | ||

I_{max} on transformed scale | Tr_I_{max} | 0.897 | 0.338^{e} | ||

Hill coefficient | γ | 4.61 | 15% (fixed)^{f} | ||

Mean turnover time of inhibition compartment | t_{out}^{g} | h | 0.940 | 95.1% | |

Maximum rate of drug release from stomach to intestine at time zero divided by dose^{h} | V_{max}(0)/dose^{h} | 1/h | 0.554^{e} | ||

Fraction of fusidic acid dose associated with 50% of V_{max}(0) | K/dose_{m}^{h} | 0.0376 | 59.2% | 18.4% | |

Fastest half-life of gastric release, if the fraction of dose in stomach is ≪K/dose_{m} | Ln(2) · K/_{m}V_{max}(0) | min | 2.82^{i} | 6.8% | 88.2% |

Mean absorption time from the intestine to the central compartment | t_{abs}^{g} | min | 33.3 | 65.0% | |

Time past last dose at which V_{max}(t) changed by 50% | TSD_{50} | h | 0.509^{c} | 20.5% | 47% |

Maximum fold change in V_{max} over time | E_{max} | 1.51^{c} | −0.978–8.93^{d} | ||

E_{max} on transformed scale | Tr_E_{max} | −1.09 | 1.99^{e} | 1.87^{e} | |

Relative extent of bioavailability with a high-fat, high-calorie breakfast | F_{fed} | 0.818 | 11.4% | ||

Ratio of V_{max}(0) in fed vs fasted state | cV_{maxfed} | 1.39 | 2.7% | ||

Ratio of K in fed vs fasted state_{m} | cK_{m}_{fed} | 0.124 | 4.3% | ||

Ratio of TC_{50} in fed vs fasted state | cTSD_{50,fed} | 1.89 | 4.4% | ||

E_{max} in fed state on untransformed scale | E_{maxfed} | 9.00^{c} | 8.97–9.00^{d} | ||

Difference of E_{max} in fed vs fasted state on transformed scale | dE_{maxfed} | 12.2 | 0.156^{e} | ||

Ratio of V_{max}(0) in evening vs morning | cV_{maxEve} | 0.324^{j} | |||

Ratio of K in evening vs morning_{m} | cK_{m}_{Eve} | 1.27^{j} | |||

Ratio of TC_{50} in evening vs morning | cTSD_{50,Eve} | 3.02^{j} | |||

E_{max} in evening on untransformed scale | E_{maxEve} | 0.733 | |||

Difference of E_{max} in evening vs morning on transformed scale | dE_{maxEve} | −0.471^{j} | |||

SD of proportional residual error | CV_{CP} | 0.143 | |||

SD of additive residual error | SD_{CP} | mg/liter | 0.319 |

↵a Relative standard errors for all variability terms could not be computed due to the complexity of the model.

↵b Estimates apply to a healthy volunteer with a total body weight of 70 kg using an allometric size model.

↵c Not an estimated parameter. Value was calculated from the other parameter estimates.

↵d Range of individual estimates.

↵e Estimate represents the standard deviation on logistically transformed scale.

↵f The between-subject variability of the Hill coefficient was fixed to a small value (15% CV) to allow estimation of the population mean using the MC-PEM algorithm.

↵g

*t*_{out}equals 1/*k*_{out};*t*_{abs}equals 1/*k*_{abs}.↵h Dose is measured in mg of fusidic acid.

↵i We estimated the ratio of

*V*_{max}(0)/*K*which represents the apparent first-order release rate constant if the fraction of drug remaining in stomach is ≪_{m}*K*/dose. The half-life of this process is reported in the table since this value is easier to interpret._{m}↵j These differences in the absorption parameters between the morning and evening doses were estimated within the between-occasion variability model. The mean of the random deviates for the evening dose was allowed to be different from 1 for

*V*_{max}(0),*K*, and TSD_{m}_{50}and different from 0 for Tr_*E*_{max}.