Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit

Scott Nyberg, Henry J. Mann, Michael Y. Hu, William D. Payne, Wei Shou Hu, Frank B. Cerra, Rory P. Remmel

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Extrahepatic drug metabolism was studied in an anhepatic rabbit model. Plasma concentrations of 4-methylumbelliferone (4-MU) and its major metabolites, 4-methylumbelliferyl-O-glucuronide and 4-mothyumbelliferyl sulfate, along with lidocaine and its major metabolites, monoethylglycinexylidide and 3-hydroxylidocaine, were measured in sham rabbits (n = 4) and anhepatic rabbits (n = 4) following bolus intravenous administration of each drug. Along with concentration profiles of the drugs and metabolites, pharmacokinetic analyses of 4-MU metabolism and lidocaine metabolism were used to assess the extrahepatic metabolism of these classical substrates. Total body clearance of 4-MU in the anhepatic rabbits was about 50% that of the sham animals. Extensive extrahepatic glucuronidation of 4-MU was revealed by comparing the AUC ratios of 4-methylumbelliferyl-O- glucuronide and 4-MU in anhepatic and sham rabbit groups. Sulfation of 4-MU was reduced significantly in the anhepatic group, although some extrahepatic sulfation was observed. Total body clearance of lidocaine was reduced 3-fold in anhepatic animals. 3-Hydroxylidocaine was only detected in plasma samples from sham animals. These results emphasize the importance of extrahepatic sites in drug metabolism, especially glucuronidation of phenolic compounds such as 4-MU.

Original languageEnglish (US)
Pages (from-to)643-648
Number of pages6
JournalDrug Metabolism and Disposition
Volume24
Issue number6
StatePublished - Jun 1 1996
Externally publishedYes

Fingerprint

Hymecromone
Lidocaine
Metabolism
Rabbits
Metabolites
Animals
Glucuronides
monoethylglycinexylidide
Pharmaceutical Preparations
Plasmas
Pharmacokinetics
Intravenous Administration
Sulfates
Area Under Curve

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Nyberg, S., Mann, H. J., Hu, M. Y., Payne, W. D., Hu, W. S., Cerra, F. B., & Remmel, R. P. (1996). Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit. Drug Metabolism and Disposition, 24(6), 643-648.

Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit. / Nyberg, Scott; Mann, Henry J.; Hu, Michael Y.; Payne, William D.; Hu, Wei Shou; Cerra, Frank B.; Remmel, Rory P.

In: Drug Metabolism and Disposition, Vol. 24, No. 6, 01.06.1996, p. 643-648.

Research output: Contribution to journalArticle

Nyberg, S, Mann, HJ, Hu, MY, Payne, WD, Hu, WS, Cerra, FB & Remmel, RP 1996, 'Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit', Drug Metabolism and Disposition, vol. 24, no. 6, pp. 643-648.
Nyberg, Scott ; Mann, Henry J. ; Hu, Michael Y. ; Payne, William D. ; Hu, Wei Shou ; Cerra, Frank B. ; Remmel, Rory P. / Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit. In: Drug Metabolism and Disposition. 1996 ; Vol. 24, No. 6. pp. 643-648.
@article{b7cd4e785c014b818e664d01fb9ccf9e,
title = "Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit",
abstract = "Extrahepatic drug metabolism was studied in an anhepatic rabbit model. Plasma concentrations of 4-methylumbelliferone (4-MU) and its major metabolites, 4-methylumbelliferyl-O-glucuronide and 4-mothyumbelliferyl sulfate, along with lidocaine and its major metabolites, monoethylglycinexylidide and 3-hydroxylidocaine, were measured in sham rabbits (n = 4) and anhepatic rabbits (n = 4) following bolus intravenous administration of each drug. Along with concentration profiles of the drugs and metabolites, pharmacokinetic analyses of 4-MU metabolism and lidocaine metabolism were used to assess the extrahepatic metabolism of these classical substrates. Total body clearance of 4-MU in the anhepatic rabbits was about 50{\%} that of the sham animals. Extensive extrahepatic glucuronidation of 4-MU was revealed by comparing the AUC ratios of 4-methylumbelliferyl-O- glucuronide and 4-MU in anhepatic and sham rabbit groups. Sulfation of 4-MU was reduced significantly in the anhepatic group, although some extrahepatic sulfation was observed. Total body clearance of lidocaine was reduced 3-fold in anhepatic animals. 3-Hydroxylidocaine was only detected in plasma samples from sham animals. These results emphasize the importance of extrahepatic sites in drug metabolism, especially glucuronidation of phenolic compounds such as 4-MU.",
author = "Scott Nyberg and Mann, {Henry J.} and Hu, {Michael Y.} and Payne, {William D.} and Hu, {Wei Shou} and Cerra, {Frank B.} and Remmel, {Rory P.}",
year = "1996",
month = "6",
day = "1",
language = "English (US)",
volume = "24",
pages = "643--648",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "6",

}

TY - JOUR

T1 - Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit

AU - Nyberg, Scott

AU - Mann, Henry J.

AU - Hu, Michael Y.

AU - Payne, William D.

AU - Hu, Wei Shou

AU - Cerra, Frank B.

AU - Remmel, Rory P.

PY - 1996/6/1

Y1 - 1996/6/1

N2 - Extrahepatic drug metabolism was studied in an anhepatic rabbit model. Plasma concentrations of 4-methylumbelliferone (4-MU) and its major metabolites, 4-methylumbelliferyl-O-glucuronide and 4-mothyumbelliferyl sulfate, along with lidocaine and its major metabolites, monoethylglycinexylidide and 3-hydroxylidocaine, were measured in sham rabbits (n = 4) and anhepatic rabbits (n = 4) following bolus intravenous administration of each drug. Along with concentration profiles of the drugs and metabolites, pharmacokinetic analyses of 4-MU metabolism and lidocaine metabolism were used to assess the extrahepatic metabolism of these classical substrates. Total body clearance of 4-MU in the anhepatic rabbits was about 50% that of the sham animals. Extensive extrahepatic glucuronidation of 4-MU was revealed by comparing the AUC ratios of 4-methylumbelliferyl-O- glucuronide and 4-MU in anhepatic and sham rabbit groups. Sulfation of 4-MU was reduced significantly in the anhepatic group, although some extrahepatic sulfation was observed. Total body clearance of lidocaine was reduced 3-fold in anhepatic animals. 3-Hydroxylidocaine was only detected in plasma samples from sham animals. These results emphasize the importance of extrahepatic sites in drug metabolism, especially glucuronidation of phenolic compounds such as 4-MU.

AB - Extrahepatic drug metabolism was studied in an anhepatic rabbit model. Plasma concentrations of 4-methylumbelliferone (4-MU) and its major metabolites, 4-methylumbelliferyl-O-glucuronide and 4-mothyumbelliferyl sulfate, along with lidocaine and its major metabolites, monoethylglycinexylidide and 3-hydroxylidocaine, were measured in sham rabbits (n = 4) and anhepatic rabbits (n = 4) following bolus intravenous administration of each drug. Along with concentration profiles of the drugs and metabolites, pharmacokinetic analyses of 4-MU metabolism and lidocaine metabolism were used to assess the extrahepatic metabolism of these classical substrates. Total body clearance of 4-MU in the anhepatic rabbits was about 50% that of the sham animals. Extensive extrahepatic glucuronidation of 4-MU was revealed by comparing the AUC ratios of 4-methylumbelliferyl-O- glucuronide and 4-MU in anhepatic and sham rabbit groups. Sulfation of 4-MU was reduced significantly in the anhepatic group, although some extrahepatic sulfation was observed. Total body clearance of lidocaine was reduced 3-fold in anhepatic animals. 3-Hydroxylidocaine was only detected in plasma samples from sham animals. These results emphasize the importance of extrahepatic sites in drug metabolism, especially glucuronidation of phenolic compounds such as 4-MU.

UR - http://www.scopus.com/inward/record.url?scp=0029952470&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029952470&partnerID=8YFLogxK

M3 - Article

VL - 24

SP - 643

EP - 648

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 6

ER -