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Research ArticleArticle

Plasma Pharmacokinetics and Tissue Distribution of aN-Pyrrolo- [1,2-c]Imidazolylphenyl Sulfonamide in Rats

Mehran F. Moghaddam, Matthew S. Bogdanffy, Alethia Brown, Kim Ford and Lamaat Shalaby
Drug Metabolism and Disposition January 2002, 30 (1) 47-54; DOI: https://doi.org/10.1124/dmd.30.1.47
Mehran F. Moghaddam
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Matthew S. Bogdanffy
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Alethia Brown
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Kim Ford
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Lamaat Shalaby
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Abstract

TY029, anN-pyrrolo[1,2-c]imidazolylphenyl sulfonamide herbicide, controls economically important weeds through inhibition of protoporphyrinogen oxygenase. As partial satisfaction of regulatory requirements to establish safety and to aid in the interpretation of toxicology bioassays, a rat metabolism study of TY029 was performed to define the pharmacokinetics and tissue distribution of this compound. Animals were exposed to single 50- and 2-mg/kg doses of [hydantoin-5-14C]TY029 by oral gavage. The tissue distribution studies revealed that generally greater than 5% of the oral dose was found in the carcass, gastrointestinal tract, liver, and the whole blood when plasma microgram equivalents per gram of TY029 was at maximum or at half of the maximum. However, these concentrations rapidly declined to negligible levels. By 96 h after the oral administration of [hydantoin-5-14C]TY029, the highest value reported for any one of the collected tissues was below 0.5% of administered dose. Therefore, neither TY029 nor its metabolites was sequestered in tissues to appreciable levels. TheCmax, Cmax/2, and area under the curve (AUCINF) obtained from the plasma pharmacokinetics suggested that in general single-dosed female rats absorbed and eliminated the test compounds faster than their male counterparts. Mass spectral evaluations of the plasma from single high- and low-dose male and female rats identified the plasma constituents related to the test compound. Although the parent molecule was present in all plasma samples, the three acidic metabolites were the predominant plasma metabolites in the high-dose groups. The overall plasma profile included TY029 and six metabolites.

Footnotes

  • Abbreviations used are::
    TY029
    anN-pyrrolo[1,2-c]imidazolylphenyl sulfonamide herbicide
    amu
    atomic mass units
    AUC
    area under the curve
    Cmax
    maximal plasma concentration
    Cmax/2
    half-maximal plasma concentration
    equiv
    equivalent
    HPLC
    high-performance liquid chromatography
    LOD
    limit of detection
    LSC
    liquid scintillation counting
    MS
    mass spectrometry
    PK
    pharmacokinetics
    SPE
    solid phase extraction
    tCmax
    time required to reach maximal plasma concentration
    tCmax/2
    time required to reach half-maximal plasma concentration
    GI
    gastrointestinal
    • Received April 26, 2001.
    • Accepted October 3, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 30 (1)
Drug Metabolism and Disposition
Vol. 30, Issue 1
1 Jan 2002
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Research ArticleArticle

Plasma Pharmacokinetics and Tissue Distribution of aN-Pyrrolo- [1,2-c]Imidazolylphenyl Sulfonamide in Rats

Mehran F. Moghaddam, Matthew S. Bogdanffy, Alethia Brown, Kim Ford and Lamaat Shalaby
Drug Metabolism and Disposition January 1, 2002, 30 (1) 47-54; DOI: https://doi.org/10.1124/dmd.30.1.47

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Research ArticleArticle

Plasma Pharmacokinetics and Tissue Distribution of aN-Pyrrolo- [1,2-c]Imidazolylphenyl Sulfonamide in Rats

Mehran F. Moghaddam, Matthew S. Bogdanffy, Alethia Brown, Kim Ford and Lamaat Shalaby
Drug Metabolism and Disposition January 1, 2002, 30 (1) 47-54; DOI: https://doi.org/10.1124/dmd.30.1.47
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