TABLE 2

Toxicokinetic parameters estimated for TA and TASO following intraperitoneal administration of 50, 300, and 600 mg/kg doses of TA

Plasma TA and TASO concentrations were determined using reversed-phase HPLC. Male Sprague-Dawley rats were treated with 50, 300, or 600 mg TA/kg via i.p. injection in saline vehicle, and plasma was collected via serial blood sampling over a time course of 0 to 1040 min. See Materials and Methods for detailed sample collection and HPLC procedure. Results are expressed as means ± S.E. (n = 3).


Parameter

Dose of Thioacetamide
50 mg/kg
300 mg/kg
600 mg/kg
TA
TASO
TA
TASO
TA
TASO
tmax (min) 5 90 5 180 5 180
Cmax (μg/ml) 30.5 ± 2.7 19.6 ± 1.12 198 ± 27.3 50.2 ± 2.42 586.8 ± 31.29 77 ± 2.9
AUC (μg · min/ml) 802 ± 9 2037 ± 71 26,509 ± 1421.6 15,443 ± 1631 141,460 ± 23,434 53,198 ± 3399
AUC/dose 16 ± 2 40.7 ± 1.4 88.4 ± 4.7 51.5 ± 5.4 235.8 ± 39.1 88.7 ± 5.7
Apparent t1/2 (min) 16 ± 1 36 ± 1.2 74.5 ± 4 81.4 ± 16.7 241.36 ± 21.6 247 ± 41.7
Plasma Clearance (1/kg · h)
1.63 ± 0.21
0.82 ± 0.06
0.30 ± 0.01
0.15 ± 0.04
0.14 ± 0.01
0.04 ± 0.01