Plasma pharmacokinetics and tissue distribution of a N-pyrrolo-[1,2-c]imidazolylphenyl sulfonamide in rats.

TY029, an N-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-(14)C]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-(14)C]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. The C(max), C(max/2), and area under the curve (AUC(INF)) 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.