Functional half-life is a meaningful descriptor of steady-state pharmacokinetics of an extended-release formulation of a rapidly cleared drug : as shown by once-daily divalproex-ER.

摘要: Background: For many drugs, steady-state concentration-time profiles are often not optimally characterised by the intrinsic terminal elimination half-life for various reasons, including multiexponential disposition with minimal contribution of phase to exposure or use controlled-release formulations extended zero- mixed zero-/first-order absorption. In such cases, ‘effective’ ‘functional’ (t1/2F) has been used characterise pharmacokinetics. Valproic acid, commonly in neuropsychiatry, an 4–16 hours different populations (children vs adults, enzyme-induced uninduced). Divalproex-ER, a once-daily extended-release divalproex sodium formulation, is designed release valproic acid over >18 hours. Hence divalproex-ER have small peak-trough fluctuations that half-life. this study, value t1/2F was calculated profiles. Methods: The t1/2F, defined as time taken concentration drop one-half during dosing interval (τ) at steady state, derived using maximum (Cmax) and minimum (Cmin) plasma τ values, ln(2)/(ln [Cmax/Cmin]/τ). values adult hepatic enzyme-uninduced healthy subjects epilepsy patients were from five pharmacokinetic studies which administered once daily 6–14 days. Results: estimated geometric mean uninduced adults 40.0 versus expected 12–16 population (including on monotherapy); induced patients, 26.9 6–12 Conclusion: characterises Cmax Cmin decrease 33% 45% following administration divalproex-ER.