Pharmacokinetics of diazepam following multiple-dose oral administration to healthy human subjects.

摘要: Six healthy subjects between the ages of 21 and 31 years received diazepam tablets orally at a dose 5 mg t.i.d. atO, 5, 10hr on days 1–13. On day 14, was 0 hr 15 10 hr. Subsequently, once daily 15–24. Numerous plasma samples were obtained during multiple-dose regimen, appropriate equations fitted to all data. Diazepam absorption satisfactorily described by first-order process, with disposition characterized linear two-compartment open model. The harmonic mean half-life 32 min, terminal exponential 57hr. apparent oral total drug clearance 22.7ml/hr/kg. Steady-state levels primary metabolite, desmethyldiazepam, reached after 5–8 dosing. concentration-time profiles suggested that administration bedtime might be satisfactory dosing regimen.