Pb. Inskeep et al., PHARMACOKINETICS OF TIQUESIDE (BETA-TIGOGENIN CELLOBIOSIDE) IN DOGS, RATS, RABBITS, AND MONKEYS, Journal of pharmaceutical sciences, 84(1), 1995, pp. 12-14
Tiqueside (CP-88,818, beta-tigogenin cellobioside) is an effective cho
lesterol absorption inhibitor that may be useful in the treatment of h
ypercholesteremia. We have investigated the pharmacokinetics of tiques
ide in dogs, rats, rabbits, and monkeys. In dogs, the volume of distri
bution (Vd(ss)) was 2.11 L/kg, clearance was 0.58 mL/min.kg, and half-
life was 45 h following a 1.4 mg/kg intravenous dose. Absolute bioavai
lability in fed dogs decreased from 6.7% for a 30 mg/kg dose to 1.7% f
or a 375 mg/kg dose. The oral bioavailability at a dose of 375 mg/kg w
as approximately 4-fold lower in fasted dogs than fed dogs. AUC-(0-24)
for doses up to 2000 mg/kg were only slightly greater than AUC-(0-24)
for a 375 mg/kg dose. In rats dosed intravenously at 8.0 mg/kg, Vd(ss
) was 3.52 L/kg, clearance was 14.6 mL/min.kg, and half-life was 3.6 h
. Estimated bioavailability for rats dosed in feed at 250-2000 mg/kg/d
ay was less than 0.5%. In rabbits dosed at 4.0 mg/kg iv, Vd(ss) was 2.
95 L/kg, clearance was 0.59 mL/min.kg, and half-life was 61 h. Bioavai
lability for rabbits dosed in feed at 62.5 or 125 mg/kg/day was approx
imately 7%. Systemic exposure in rhesus monkeys after oral dosing was
lower than that for dogs and rabbits. Thus, low systemic exposure to t
iqueside following oral administration has been demonstrated in severa
l animal species.