PBA-ω-Lys as sustained phenylbutyrate-releasing prodrug

Chun Li Wang, Po Ren Hsueh, Meng Jie Sun, Yann Lii Leu, Feng Shou Chang, Shu Wei Yang, Jang Feng Lian, Hui Po Wang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Lysine was attached to phenylbutyric acid (PBA) to form PBA-α-Lys and PBA-ω-Lys as PBA prodrugs for treating chemotherapy-associated mucositis. Pharmacokinetic studies were conducted in Wistar rats for determining the systemic bioavailability of both prodrugs and the released PBA. The systemic bioavailability of PBA after oral administration of PBA-α-Lys or PBA-ω-Lys was higher than from i.v. administration, indicating that first pass effect is responsible for the transformation from the prodrugs to the parent drug. Lack of stability in the intestine made PBA-α-Lys unsatisfied as an oral prodrug of PBA. Oral administration of PBA-ω-Lys, on the other hand, led to a slow PBA-releasing profile in circulation. Although the AUC 0→t of systemic released PBA from oral administration of PBA-ω-Lys was lower than from oral administration of PBA per se, MRT inf was 5 times longer (9.64 ± 2.16 vs 1.81 ± 0.28 hr), t1/2 was 4 times longer (6.18 ± 2.09 hr vs 1.50 ± 0.17 hr), and AUMCinf was 2 folds higher (168.7 ± 67.7 hr*h*μg/mL vs 88.8 ± 12.4 hr*h*μg/mL). In conclusion, oral administration of PBA-ω-Lysine exhibited a sustained PBA-releasing pharmacokinetic profile in rats. The bioavailability of PBA released in inflammatory tissues and anti-mucositis activity need to be further investigated for the evaluation of PBA-ω-Lysine as an effective targetable anti-mucositis agent.

Original languageEnglish
Pages (from-to)371-379
Number of pages9
JournalJournal of Food and Drug Analysis
Volume18
Issue number6
Publication statusPublished - Dec 2010

Fingerprint

Phenylbutyrates
Prodrugs
Acids
acids
oral administration
Oral Administration
Mucositis
Biological Availability
Lysine
bioavailability
lysine
pharmacokinetics
Pharmacokinetics

Keywords

  • PBA-α-Lys
  • PBA-ω-Lys
  • Pharmacokinetics
  • Phenylbutyric acid

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

Cite this

Wang, C. L., Hsueh, P. R., Sun, M. J., Leu, Y. L., Chang, F. S., Yang, S. W., ... Wang, H. P. (2010). PBA-ω-Lys as sustained phenylbutyrate-releasing prodrug. Journal of Food and Drug Analysis, 18(6), 371-379.

PBA-ω-Lys as sustained phenylbutyrate-releasing prodrug. / Wang, Chun Li; Hsueh, Po Ren; Sun, Meng Jie; Leu, Yann Lii; Chang, Feng Shou; Yang, Shu Wei; Lian, Jang Feng; Wang, Hui Po.

In: Journal of Food and Drug Analysis, Vol. 18, No. 6, 12.2010, p. 371-379.

Research output: Contribution to journalArticle

Wang, CL, Hsueh, PR, Sun, MJ, Leu, YL, Chang, FS, Yang, SW, Lian, JF & Wang, HP 2010, 'PBA-ω-Lys as sustained phenylbutyrate-releasing prodrug', Journal of Food and Drug Analysis, vol. 18, no. 6, pp. 371-379.
Wang CL, Hsueh PR, Sun MJ, Leu YL, Chang FS, Yang SW et al. PBA-ω-Lys as sustained phenylbutyrate-releasing prodrug. Journal of Food and Drug Analysis. 2010 Dec;18(6):371-379.
Wang, Chun Li ; Hsueh, Po Ren ; Sun, Meng Jie ; Leu, Yann Lii ; Chang, Feng Shou ; Yang, Shu Wei ; Lian, Jang Feng ; Wang, Hui Po. / PBA-ω-Lys as sustained phenylbutyrate-releasing prodrug. In: Journal of Food and Drug Analysis. 2010 ; Vol. 18, No. 6. pp. 371-379.
@article{f11cbf95d30348b1bcaebdf8717b78f8,
title = "PBA-ω-Lys as sustained phenylbutyrate-releasing prodrug",
abstract = "Lysine was attached to phenylbutyric acid (PBA) to form PBA-α-Lys and PBA-ω-Lys as PBA prodrugs for treating chemotherapy-associated mucositis. Pharmacokinetic studies were conducted in Wistar rats for determining the systemic bioavailability of both prodrugs and the released PBA. The systemic bioavailability of PBA after oral administration of PBA-α-Lys or PBA-ω-Lys was higher than from i.v. administration, indicating that first pass effect is responsible for the transformation from the prodrugs to the parent drug. Lack of stability in the intestine made PBA-α-Lys unsatisfied as an oral prodrug of PBA. Oral administration of PBA-ω-Lys, on the other hand, led to a slow PBA-releasing profile in circulation. Although the AUC 0→t of systemic released PBA from oral administration of PBA-ω-Lys was lower than from oral administration of PBA per se, MRT inf was 5 times longer (9.64 ± 2.16 vs 1.81 ± 0.28 hr), t1/2 was 4 times longer (6.18 ± 2.09 hr vs 1.50 ± 0.17 hr), and AUMCinf was 2 folds higher (168.7 ± 67.7 hr*h*μg/mL vs 88.8 ± 12.4 hr*h*μg/mL). In conclusion, oral administration of PBA-ω-Lysine exhibited a sustained PBA-releasing pharmacokinetic profile in rats. The bioavailability of PBA released in inflammatory tissues and anti-mucositis activity need to be further investigated for the evaluation of PBA-ω-Lysine as an effective targetable anti-mucositis agent.",
keywords = "PBA-α-Lys, PBA-ω-Lys, Pharmacokinetics, Phenylbutyric acid",
author = "Wang, {Chun Li} and Hsueh, {Po Ren} and Sun, {Meng Jie} and Leu, {Yann Lii} and Chang, {Feng Shou} and Yang, {Shu Wei} and Lian, {Jang Feng} and Wang, {Hui Po}",
year = "2010",
month = "12",
language = "English",
volume = "18",
pages = "371--379",
journal = "Journal of Food and Drug Analysis",
issn = "1021-9498",
publisher = "Elsevier Taiwan LLC",
number = "6",

}

TY - JOUR

T1 - PBA-ω-Lys as sustained phenylbutyrate-releasing prodrug

AU - Wang, Chun Li

AU - Hsueh, Po Ren

AU - Sun, Meng Jie

AU - Leu, Yann Lii

AU - Chang, Feng Shou

AU - Yang, Shu Wei

AU - Lian, Jang Feng

AU - Wang, Hui Po

PY - 2010/12

Y1 - 2010/12

N2 - Lysine was attached to phenylbutyric acid (PBA) to form PBA-α-Lys and PBA-ω-Lys as PBA prodrugs for treating chemotherapy-associated mucositis. Pharmacokinetic studies were conducted in Wistar rats for determining the systemic bioavailability of both prodrugs and the released PBA. The systemic bioavailability of PBA after oral administration of PBA-α-Lys or PBA-ω-Lys was higher than from i.v. administration, indicating that first pass effect is responsible for the transformation from the prodrugs to the parent drug. Lack of stability in the intestine made PBA-α-Lys unsatisfied as an oral prodrug of PBA. Oral administration of PBA-ω-Lys, on the other hand, led to a slow PBA-releasing profile in circulation. Although the AUC 0→t of systemic released PBA from oral administration of PBA-ω-Lys was lower than from oral administration of PBA per se, MRT inf was 5 times longer (9.64 ± 2.16 vs 1.81 ± 0.28 hr), t1/2 was 4 times longer (6.18 ± 2.09 hr vs 1.50 ± 0.17 hr), and AUMCinf was 2 folds higher (168.7 ± 67.7 hr*h*μg/mL vs 88.8 ± 12.4 hr*h*μg/mL). In conclusion, oral administration of PBA-ω-Lysine exhibited a sustained PBA-releasing pharmacokinetic profile in rats. The bioavailability of PBA released in inflammatory tissues and anti-mucositis activity need to be further investigated for the evaluation of PBA-ω-Lysine as an effective targetable anti-mucositis agent.

AB - Lysine was attached to phenylbutyric acid (PBA) to form PBA-α-Lys and PBA-ω-Lys as PBA prodrugs for treating chemotherapy-associated mucositis. Pharmacokinetic studies were conducted in Wistar rats for determining the systemic bioavailability of both prodrugs and the released PBA. The systemic bioavailability of PBA after oral administration of PBA-α-Lys or PBA-ω-Lys was higher than from i.v. administration, indicating that first pass effect is responsible for the transformation from the prodrugs to the parent drug. Lack of stability in the intestine made PBA-α-Lys unsatisfied as an oral prodrug of PBA. Oral administration of PBA-ω-Lys, on the other hand, led to a slow PBA-releasing profile in circulation. Although the AUC 0→t of systemic released PBA from oral administration of PBA-ω-Lys was lower than from oral administration of PBA per se, MRT inf was 5 times longer (9.64 ± 2.16 vs 1.81 ± 0.28 hr), t1/2 was 4 times longer (6.18 ± 2.09 hr vs 1.50 ± 0.17 hr), and AUMCinf was 2 folds higher (168.7 ± 67.7 hr*h*μg/mL vs 88.8 ± 12.4 hr*h*μg/mL). In conclusion, oral administration of PBA-ω-Lysine exhibited a sustained PBA-releasing pharmacokinetic profile in rats. The bioavailability of PBA released in inflammatory tissues and anti-mucositis activity need to be further investigated for the evaluation of PBA-ω-Lysine as an effective targetable anti-mucositis agent.

KW - PBA-α-Lys

KW - PBA-ω-Lys

KW - Pharmacokinetics

KW - Phenylbutyric acid

UR - http://www.scopus.com/inward/record.url?scp=79952461742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952461742&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:79952461742

VL - 18

SP - 371

EP - 379

JO - Journal of Food and Drug Analysis

JF - Journal of Food and Drug Analysis

SN - 1021-9498

IS - 6

ER -