PMID- 23190215
OWN - NLM
STAT- MEDLINE
DCOM- 20130304
LR  - 20131121
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Linking)
VI  - 54
IP  - 1
DP  - 2013 Jan
TI  - Extended-release antiepileptic drugs: a comparison of pharmacokinetic parameters 
      relative to original immediate-release formulations.
PG  - 28-35
LID - 10.1111/epi.12043 [doi]
AB  - Many antiepileptic drugs (AEDs) have short half-lives with large fluctuations in 
      peak-to-trough plasma concentrations. Consequences of these pharmacokinetic (PK) 
      properties may include adverse events (AEs) and breakthrough seizures, 
      potentially leading to poor adherence. To address these challenges, newer 
      formulations of these AEDs have been developed using unique extended-release (ER) 
      technologies. These technologies extend the dosing interval such that dosing 
      frequency can be minimized, which may improve patient adherence. Available ER 
      formulations have the potential to minimize the spikes in maximum plasma 
      concentrations (C(max) ) at steady-state that often contribute to AEs during 
      treatment with immediate-release (IR) products. In so doing, tolerability 
      advantages may lead to increased AED effectiveness by improving adherence and 
      allowing higher doses if clinically indicated. Direct PK comparison studies of IR 
      and ER formulations (e.g., carbamazepine, divalproate sodium, lamotrigine, 
      oxcarbazepine, levetiracetam, and phenytoin) have found that dose-normalized ER 
      formulations may or may not be bioequivalent to their IR counterparts, but most 
      ER formulations have a lower fluctuation index ([C(max) -C(min) ]/C(avg) ) 
      compared with the IR versions. This results in flatter concentration-time plots. 
      Not all ER preparations improve the various PK parameters to the same extent, and 
      PK nuances may impact the effectiveness, tolerability, and adherence rates of 
      various ER formulations.
CI  - Wiley Periodicals, Inc. (c) 2012 International League Against Epilepsy.
FAU - Leppik, Ilo E
AU  - Leppik IE
AD  - MINCEP Epilepsy Care, Minneapolis, Minnesota 55414, USA. leppi001@umn.edu
FAU - Hovinga, Collin A
AU  - Hovinga CA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Review
DEP - 20121128
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 0 (Delayed-Action Preparations)
RN  - 33CM23913M (Carbamazepine)
RN  - 614OI1Z5WI (Valproic Acid)
SB  - IM
MH  - Anticonvulsants/*administration & dosage/pharmacokinetics/therapeutic use
MH  - Carbamazepine/administration & dosage/pharmacokinetics/therapeutic use
MH  - Delayed-Action Preparations
MH  - Drug Tolerance
MH  - Epilepsy/drug therapy
MH  - Humans
MH  - Valproic Acid/administration & dosage/pharmacokinetics/therapeutic use
EDAT- 2012/11/30 06:00
MHDA- 2013/03/05 06:00
CRDT- 2012/11/30 06:00
PHST- 2012/11/30 06:00 [entrez]
PHST- 2012/11/30 06:00 [pubmed]
PHST- 2013/03/05 06:00 [medline]
AID - 10.1111/epi.12043 [doi]
PST - ppublish
SO  - Epilepsia. 2013 Jan;54(1):28-35. doi: 10.1111/epi.12043. Epub 2012 Nov 28.