Pharmacokinetics of oltipraz in mutant Nagase analbuminemic rats

Soo K. Bae; Hee E. Kang; Min K. Kang; Jin W. Kim; Taekrho Kim; Myung G. Lee

doi:10.1002/jps.20602

Pharmacokinetics of oltipraz in mutant Nagase analbuminemic rats

Soo K. Bae
, Hee E. Kang
, Min K. Kang
, Jin W. Kim
, Taekrho Kim
, Myung G. Lee

Pharmacy

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

5 Scopus citations

Abstract

Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (50 mg/kg) administration to control male Sprague-Dawely rats and mutant Nagase analbuminemic rats (NARs). In NARs, the expression and mRNA level of CYP1A2 increased, and oltipraz was mainly metabolized via CYP1A1/2, 2B1/2, 2C11, 201, and 3A1/2 in male rats. Hence, it may be expected that the CL of oltipraz would be significantly faster in NARs. This was proven by the following results. After intravenous administration, the CL of oltipraz was significantly faster in NARs (125% increase) than controls due to significantly greater free fractions (unbound to plasma proteins) of oltipraz (197% increase) and significantly faster CL_int for the disappearance of oltipraz (11.4% increase) in NARs, since oltipraz is an intermediate hepatic extraction ratio drug in rats. The V_ss was significantly larger in NARs (109% increase) and this could be due to significant increase in free fractions of oltipraz in NARs. After oral administration, the AUC of oltipraz was also significantly smaller in NARs (61.9% decrease). This could also be due to significant increase in free fractions of oltipraz and significantly faster CL_int in NARs. However, this was not due to decrease in absorption in NARs.

Original language	English
Pages (from-to)	998-1005
Number of pages	8
Journal	Journal of Pharmaceutical Sciences
Volume	95
Issue number	5
DOIs	https://doi.org/10.1002/jps.20602
State	Published - May 2006

Bibliographical note

Funding Information:
This study was supported in part by a grant from the Korea Ministry of Health & Welfare, Korea, 02-PJ2-PG4-PT01-0027, 2005–2006.

Keywords

CYP enzymes
CYP1A2
Metabolism
Mutant Nagase analbuminemic rats
Oltipraz
Pharmacokinetics
Protein binding

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10.1002/jps.20602

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@article{d779b361637949149051b5dd166dc32b,

title = "Pharmacokinetics of oltipraz in mutant Nagase analbuminemic rats",

abstract = "Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (50 mg/kg) administration to control male Sprague-Dawely rats and mutant Nagase analbuminemic rats (NARs). In NARs, the expression and mRNA level of CYP1A2 increased, and oltipraz was mainly metabolized via CYP1A1/2, 2B1/2, 2C11, 201, and 3A1/2 in male rats. Hence, it may be expected that the CL of oltipraz would be significantly faster in NARs. This was proven by the following results. After intravenous administration, the CL of oltipraz was significantly faster in NARs (125\% increase) than controls due to significantly greater free fractions (unbound to plasma proteins) of oltipraz (197\% increase) and significantly faster CLint for the disappearance of oltipraz (11.4\% increase) in NARs, since oltipraz is an intermediate hepatic extraction ratio drug in rats. The Vss was significantly larger in NARs (109\% increase) and this could be due to significant increase in free fractions of oltipraz in NARs. After oral administration, the AUC of oltipraz was also significantly smaller in NARs (61.9\% decrease). This could also be due to significant increase in free fractions of oltipraz and significantly faster CLint in NARs. However, this was not due to decrease in absorption in NARs.",

keywords = "CYP enzymes, CYP1A2, Metabolism, Mutant Nagase analbuminemic rats, Oltipraz, Pharmacokinetics, Protein binding",

author = "Bae, \{Soo K.\} and Kang, \{Hee E.\} and Kang, \{Min K.\} and Kim, \{Jin W.\} and Taekrho Kim and Lee, \{Myung G.\}",

note = "Funding Information: This study was supported in part by a grant from the Korea Ministry of Health \& Welfare, Korea, 02-PJ2-PG4-PT01-0027, 2005–2006.",

year = "2006",

month = may,

doi = "10.1002/jps.20602",

language = "English",

volume = "95",

pages = "998--1005",

journal = "Journal of Pharmaceutical Sciences",

issn = "0022-3549",

publisher = "Elsevier B.V.",

number = "5",

}

TY - JOUR

T1 - Pharmacokinetics of oltipraz in mutant Nagase analbuminemic rats

AU - Bae, Soo K.

AU - Kang, Hee E.

AU - Kang, Min K.

AU - Kim, Jin W.

AU - Kim, Taekrho

AU - Lee, Myung G.

N1 - Funding Information: This study was supported in part by a grant from the Korea Ministry of Health & Welfare, Korea, 02-PJ2-PG4-PT01-0027, 2005–2006.

PY - 2006/5

Y1 - 2006/5

N2 - Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (50 mg/kg) administration to control male Sprague-Dawely rats and mutant Nagase analbuminemic rats (NARs). In NARs, the expression and mRNA level of CYP1A2 increased, and oltipraz was mainly metabolized via CYP1A1/2, 2B1/2, 2C11, 201, and 3A1/2 in male rats. Hence, it may be expected that the CL of oltipraz would be significantly faster in NARs. This was proven by the following results. After intravenous administration, the CL of oltipraz was significantly faster in NARs (125% increase) than controls due to significantly greater free fractions (unbound to plasma proteins) of oltipraz (197% increase) and significantly faster CLint for the disappearance of oltipraz (11.4% increase) in NARs, since oltipraz is an intermediate hepatic extraction ratio drug in rats. The Vss was significantly larger in NARs (109% increase) and this could be due to significant increase in free fractions of oltipraz in NARs. After oral administration, the AUC of oltipraz was also significantly smaller in NARs (61.9% decrease). This could also be due to significant increase in free fractions of oltipraz and significantly faster CLint in NARs. However, this was not due to decrease in absorption in NARs.

AB - Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (50 mg/kg) administration to control male Sprague-Dawely rats and mutant Nagase analbuminemic rats (NARs). In NARs, the expression and mRNA level of CYP1A2 increased, and oltipraz was mainly metabolized via CYP1A1/2, 2B1/2, 2C11, 201, and 3A1/2 in male rats. Hence, it may be expected that the CL of oltipraz would be significantly faster in NARs. This was proven by the following results. After intravenous administration, the CL of oltipraz was significantly faster in NARs (125% increase) than controls due to significantly greater free fractions (unbound to plasma proteins) of oltipraz (197% increase) and significantly faster CLint for the disappearance of oltipraz (11.4% increase) in NARs, since oltipraz is an intermediate hepatic extraction ratio drug in rats. The Vss was significantly larger in NARs (109% increase) and this could be due to significant increase in free fractions of oltipraz in NARs. After oral administration, the AUC of oltipraz was also significantly smaller in NARs (61.9% decrease). This could also be due to significant increase in free fractions of oltipraz and significantly faster CLint in NARs. However, this was not due to decrease in absorption in NARs.

KW - CYP enzymes

KW - CYP1A2

KW - Metabolism

KW - Mutant Nagase analbuminemic rats

KW - Oltipraz

KW - Pharmacokinetics

KW - Protein binding

UR - https://www.scopus.com/pages/publications/33646542739

U2 - 10.1002/jps.20602

DO - 10.1002/jps.20602

M3 - Article

C2 - 16544321

AN - SCOPUS:33646542739

SN - 0022-3549

VL - 95

SP - 998

EP - 1005

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

IS - 5

ER -

Pharmacokinetics of oltipraz in mutant Nagase analbuminemic rats

Abstract

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Keywords

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