Related Experiment Video
Updated: Aug 9, 2026
10:17
High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
Comparative absorption profiles of divalproex sodium delayed-release versus extended-release tablets -- clinical
Sandeep Dutta1, Ronald C Reed, Robert F O'Dea
1Clinical Pharmacokinetics, Abbott Laboratories, Abbott Park, IL 60064, USA. Sandeep.Dutta@abbott.com
The Annals of Pharmacotherapy
|March 30, 2006
Summary
Divalproex sodium extended-release (ER) offers immediate, slow absorption over 20 hours, unlike delayed-release (DR) which has a 2-hour lag time and rapid absorption. Both formulations achieve complete valproic acid (VPA) absorption.
Area of Science:
- Pharmacokinetics
- Drug Delivery Systems
- Clinical Pharmacology
Background:
- Divalproex sodium is available in delayed-release (DR) and extended-release (ER) formulations.
- The distinct absorption profiles of these divalproex sodium formulations are not widely recognized.
Purpose of the Study:
- To quantitatively and qualitatively differentiate the absorption characteristics of divalproex-DR and divalproex-ER formulations.
- To compare the pharmacokinetic profiles of valproic acid (VPA) from both formulations.
Main Methods:
- A crossover study involving 28 healthy volunteers.
- Single 1000 mg doses of divalproex-DR and divalproex-ER were administered.
- Pharmacokinetic analysis of VPA plasma concentrations over 48 hours using noncompartmental and compartmental models.
Main Results:
- Divalproex-DR showed a 2-hour lag time before VPA absorption, with rapid absorption occurring within 6-7 hours.
- Divalproex-ER demonstrated immediate VPA absorption starting at a modest rate, continuing slowly and constantly for over 20 hours.
- Complete VPA absorption for DR was approximately 93%, while ER showed complete absorption over 20 hours without dose dumping.
Conclusions:
- VPA absorption from divalproex-DR is rapid after a 2-hour lag time, completing within 6-7 hours.
- VPA absorption from divalproex-ER begins immediately and proceeds at a slow, constant rate for over 20 hours.
Related Concept Videos
01:30Modified-Release Drug Delivery Systems: Bioavailability
Modified-release (MR) dosage forms are designed to extend drug release over time, thereby maintaining stable plasma concentrations and reducing dosing frequency. However, their bioavailability is typically below 100% due to incomplete drug release and presystemic metabolism, and limitations in drug permeability across the gastrointestinal epithelium, all of which can restrict the fraction of the drug reaching systemic circulation. Consequently, studying the in vivo bioavailability of MR...
01:19Modified-Release Drug Delivery Systems: Overview
Modified-release dosage forms are designed to address the limitations of drugs with short biological half-lives. These forms maintain stable therapeutic drug concentrations over extended periods, reducing the need for frequent dosing. A consistent drug level helps minimize peak-trough fluctuations, which can reduce adverse effects, lower the risk of drug resistance, and improve overall treatment effectiveness.One common type of modified-release form is the extended-release (ER) formulation. ER...
01:22Modified-Release Drug Delivery Systems: Drug Release Characteristics
Drug release from modified-release dosage forms is designed to achieve specific therapeutic effects by controlling the rate and extent of drug release. The classification of these drug release systems is based on key pharmacokinetic assumptions: drug disposition follows first-order kinetics, drug release is the rate-limiting step in absorption, and the released drug is rapidly and completely absorbed.There are four major models of drug release patterns. The first model is the slow zero-order...
01:14Drug Dissolution: Requirements and Profile Comparison
The acceptance criteria for dissolution profile data are anchored in Q values, representing the percentage of drug dissolved within a specified period. This assessment unfolds in three stages:First Stage: The test passes if all six drug dosage units are equal to or greater than Q plus 5%; otherwise, the sample proceeds to the second stage.Second Stage: The average of twelve units must be equal to or greater than Q, with no unit falling below Q - 15% to pass; if not, it progresses to the final...
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
01:26Oral Drug Delivery Systems: Continuous-Release Systems
Continuous-release drug delivery systems offer a strategic approach to maintaining therapeutic drug levels over extended periods following oral administration. By modulating the release rate of active pharmaceutical ingredients, these systems minimize fluctuations in plasma concentrations, which enhances clinical efficacy and reduces the need for frequent dosing. Such characteristics make them particularly advantageous in managing chronic diseases where patient adherence and stable drug...