Pharmacokinetics of sulfluramid and its metabolite desethylsulfluramid after intravenous and intraruminal administration of sulfluramid to sheep

Pharmacokinetic properties and tissue residues of the insecticide sulfluramid (I) and its major metabolite desethylsulfluramid (II) were determined in healthy sheep after bolus intravenous (IV) administration (5 and 15 mg kg⁻¹; n = 10) and bolus intraruminal (IR) administration (100 and 400 mg kg⁻¹; n = 12) of I . Depression, lethargy, and dyspnea were noted for 4 h after the higher IV dose, but not after the other IV or IR doses. The time courses of the mean blood concentrations of I and II were best described by a two-compartment open model with rapid distribution and slow elimination phases. The blood-to-plasma concentration ratios for I and II were 1.43 (± 0.50) and 26.7 (± 9.41), respectively, suggesting binding of II to red blood cells. The T_1/2β values for I and II for the higher IV dose of I were 15.3 (± 4.68) h and 63.4 (± 4.75) h and for the higher IR dose of I , 31.5 (± 5.41) h and 74.9 (± 7.49) h, respectively. Bioavailability was 28.6 (± 2.96)% for the lower IR dose and 19.5 (± 0.99)% for the higher IR dose. C_max values for II were higher in female than male sheep after IR administration of I . Only II was found in tissue samples, with the highest concentration being in liver (9.4 (± 5.2) µg g⁻¹). © 1999 Society of Chemical Industry