Kinetics of N-[(4-chlorophenyl)amino]carbonyl-2,3-dihydro-1H-indene-5-sulfonamide (LY186641) in humans.

Abstract

The metabolism and disposition of LY186641, a diarylsulfonylurea with antineoplastic activity identified in preclinical tests, was determined in 21 patients who received 23 courses of orally administered drug. A linear correlation was found between the dose of drug administered and LY186641 peak plasma concentrations and LY186641 area under the curve measurements. Clearance (135 +/- 36 ml/h/m2), terminal half-life (31 +/- 11 h), and volume of distribution (10.2 +/- 2.8 liters) were independent of drug dose. No LY186641 was excreted in urine. Hydroxy and keto metabolites of LY186641 were identified in plasma and urine samples. Urinary excretion of these metabolites during the initial 48 h following drug administration accounted for 20% of LY186641 disposition. Plasma half-life of the hydroxy and keto metabolites was longer than that of parent drug (3.3 and 3.1 days, respectively). Plasma concentrations of parent drug correlated with the presence of methemoglobinemia, the dose-limiting toxicity found with LY186641.

• Authors: K R Hande, J Kuttesch, M Hamilton, W Satterlee, L Jackson, G Grindey, J D Hainsworth
• Journal: Cancer research (Cancer Res) Vol. 50 Issue 13 Pg. 3910-4 (Jul 01 1990) ISSN: 0008-5472 [Print] United States
• PMID: 2354440 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Sulfonylurea Compounds
• sulofenur

Topics

• Administration, Oral
• Half-Life
• Humans
• Methemoglobinemia (chemically induced)
• Neoplasms (metabolism)
• Sulfonylurea Compounds (administration & dosage, adverse effects, blood, pharmacokinetics)
• Time Factors