ArticleClinical drug investigation2006
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.
Article in Clinical drug investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
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- Population pharmacokinetics of daclizumab high-yield process in healthy volunteers: integrated analysis of intravenous and subcutaneous, single- and multiple-dose administration.Clinical pharmacokinetics · 2014Trial
- Efficacy of monotherapy with zonisamide and proposed reference interval in dogs with epilepsy: a cohort of 207 dogs (2011-2021).Journal of veterinary internal medicine · 2026Article
- Severe Pancytopenia Induced by Valproic Acid.Cureus · 2020Article
- In utero exposure to valproic acid disrupts ascending projections to the central nucleus of the inferior colliculus from the auditory brainstem.Experimental brain research · 2020Article
- Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for valproic acid and divalproex.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Article
- Prenatal exposure to valproic acid increases miR-132 levels in the mouse embryonic brain.Molecular autism · 2017Article
- Clarification of contraceptive drug pharmacokinetics in obesity.Contraception · 2017Review
- Perspectives on variability in pharmacokinetics of an oral contraceptive product.Contraception · 2017Review
- The role of 5-HT1A receptors in mediating acute negative effects of antidepressants: implications in pediatric depression.Translational psychiatry · 2015Article
- Pharmacotherapeutics of epilepsy: use of lamotrigine and expectations for lamotrigine extended release.Therapeutics and clinical risk management · 2008Article
- A Clinician's Guide to Oral Extended-Release Drug Delivery Systems in Epilepsy.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAGReview
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2 authors at 1 institution in 1 country.
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Abstract
backgroundFor 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 the terminal phase to steady-state exposure or use of controlled-release formulations with extended zero- or mixed zero-/first-order absorption. In such cases, 'effective' or 'functional' half-life (t((1/2)F)) has often been used to characterise steady-state pharmacokinetics. Valproic acid, commonly used in neuropsychiatry, has an elimination half-life of 4-16 hours in different populations (children vs adults, enzyme-induced vs uninduced). Divalproex-ER, a once-daily extended- release divalproex sodium formulation, is designed to release valproic acid over >18 hours. Hence the steady-state divalproex-ER concentration-time profiles have small peak-trough fluctuations that are not optimally characterised by valproic acid elimination half-life. In this study, the value of t((1/2)F) was calculated to characterise divalproex-ER steady-state concentration-time profiles.
methodsThe value of t((1/2)F), defined as the time taken for the concentration to drop by one-half during a dosing interval (tau) at steady state, was derived using steady-state maximum (C(max)) and minimum (C(min)) plasma concentration and tau values, and calculated as ln(2)/(ln [C(max)/C(min)]/tau). The t((1/2)F) values of valproic acid in adult hepatic enzyme-uninduced healthy subjects and enzyme-induced epilepsy patients were calculated from five pharmacokinetic studies in which divalproex-ER was administered once daily for 6-14 days.
resultsThe estimated geometric mean t((1/2)F) in uninduced adults was 40.0 hours versus the expected elimination half-life of 12-16 hours in this population (including patients on valproic acid monotherapy); for induced patients, t((1/2)F) was 26.9 hours versus the expected elimination half-life of 6-12 hours.
conclusionThe t((1/2)F) of valproic acid optimally characterises the expected steady-state C(max) to C(min )decrease of 33% in uninduced and 45% in induced adults following once-daily administration of divalproex-ER.
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