Pharmacokinetic analysis of valdice - a diethylcarbonate prodrug of valproic acid

Meir Bialer; Zharura Pharaj; Shulamit Zuckerman; Itamar Raz; Oded Abramsky; Jeff Sterling; David Ladkani

doi:10.1016/0928-0987(94)90028-0

Pharmacokinetic analysis of valdice - a diethylcarbonate prodrug of valproic acid

Meir Bialer^*
, Zharura Pharaj
, Shulamit Zuckerman
, Itamar Raz
, Oded Abramsky
, Jeff Sterling
, David Ladkani

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

The pharmacokinetics of valdice, a new diethylcarbonate prodrug of valproic acid (VPA), was investigated in humans and dogs. In both species valdice was biotransformed to VPA and no valdice was detected in the plasma following its oral administration. The relative bioavailability of VPA following oral administration of valdice was 79% in dogs and 94-99% in humans, in comparison to commercially available tablets of VPA. In humans valdice showed a longer tmax value than two commercial enteric coated products of VPA, Depakine 500 and Depakote. Nevertheless, the MRT values of the three investigated VPA products were similar. The current study showed that in humans valdice exhibited a controlled rate of delivery of VPA although it did not show an in vivo sustained release performance like a once daily sustained release (SR) product of VPA.

Original language	English
Pages (from-to)	239-244
Number of pages	6
Journal	European Journal of Pharmaceutical Sciences
Volume	2
Issue number	3
DOIs	https://doi.org/10.1016/0928-0987(94)90028-0
State	Published - Oct 1994

Keywords

Dogs
Humans
Prodrug
Valdice, pharmacokinetic evaluation
Valproic acid

Access to Document

10.1016/0928-0987(94)90028-0

Cite this

@article{cc8a04019f64450cb55ecdb3c703990d,

title = "Pharmacokinetic analysis of valdice - a diethylcarbonate prodrug of valproic acid",

abstract = "The pharmacokinetics of valdice, a new diethylcarbonate prodrug of valproic acid (VPA), was investigated in humans and dogs. In both species valdice was biotransformed to VPA and no valdice was detected in the plasma following its oral administration. The relative bioavailability of VPA following oral administration of valdice was 79\% in dogs and 94-99\% in humans, in comparison to commercially available tablets of VPA. In humans valdice showed a longer tmax value than two commercial enteric coated products of VPA, Depakine 500 and Depakote. Nevertheless, the MRT values of the three investigated VPA products were similar. The current study showed that in humans valdice exhibited a controlled rate of delivery of VPA although it did not show an in vivo sustained release performance like a once daily sustained release (SR) product of VPA.",

keywords = "Dogs, Humans, Prodrug, Valdice, pharmacokinetic evaluation, Valproic acid",

author = "Meir Bialer and Zharura Pharaj and Shulamit Zuckerman and Itamar Raz and Oded Abramsky and Jeff Sterling and David Ladkani",

year = "1994",

month = oct,

doi = "10.1016/0928-0987(94)90028-0",

language = "אנגלית",

volume = "2",

pages = "239--244",

journal = "European Journal of Pharmaceutical Sciences",

issn = "0928-0987",

publisher = "Elsevier B.V.",

number = "3",

}

TY - JOUR

T1 - Pharmacokinetic analysis of valdice - a diethylcarbonate prodrug of valproic acid

AU - Bialer, Meir

AU - Pharaj, Zharura

AU - Zuckerman, Shulamit

AU - Raz, Itamar

AU - Abramsky, Oded

AU - Sterling, Jeff

AU - Ladkani, David

PY - 1994/10

Y1 - 1994/10

N2 - The pharmacokinetics of valdice, a new diethylcarbonate prodrug of valproic acid (VPA), was investigated in humans and dogs. In both species valdice was biotransformed to VPA and no valdice was detected in the plasma following its oral administration. The relative bioavailability of VPA following oral administration of valdice was 79% in dogs and 94-99% in humans, in comparison to commercially available tablets of VPA. In humans valdice showed a longer tmax value than two commercial enteric coated products of VPA, Depakine 500 and Depakote. Nevertheless, the MRT values of the three investigated VPA products were similar. The current study showed that in humans valdice exhibited a controlled rate of delivery of VPA although it did not show an in vivo sustained release performance like a once daily sustained release (SR) product of VPA.

AB - The pharmacokinetics of valdice, a new diethylcarbonate prodrug of valproic acid (VPA), was investigated in humans and dogs. In both species valdice was biotransformed to VPA and no valdice was detected in the plasma following its oral administration. The relative bioavailability of VPA following oral administration of valdice was 79% in dogs and 94-99% in humans, in comparison to commercially available tablets of VPA. In humans valdice showed a longer tmax value than two commercial enteric coated products of VPA, Depakine 500 and Depakote. Nevertheless, the MRT values of the three investigated VPA products were similar. The current study showed that in humans valdice exhibited a controlled rate of delivery of VPA although it did not show an in vivo sustained release performance like a once daily sustained release (SR) product of VPA.

KW - Dogs

KW - Humans

KW - Prodrug

KW - Valdice, pharmacokinetic evaluation

KW - Valproic acid

UR - https://www.scopus.com/pages/publications/0028152556

U2 - 10.1016/0928-0987(94)90028-0

DO - 10.1016/0928-0987(94)90028-0

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:0028152556

SN - 0928-0987

VL - 2

SP - 239

EP - 244

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

IS - 3

ER -

Pharmacokinetic analysis of valdice - a diethylcarbonate prodrug of valproic acid

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this