Pharmacokinetics of tiqueside (β‐tigogenin cellobioside) in dogs, rats, rabbits, and monkeys

Philip B. Inskeep, Ann G. Connolly, Mark J. Cole, Elbridge W. Luther, B. Michael Silber, Michael L. Biehl, Carol A. Marzetta, Yvette E. Savoy

Research output: Contribution to journalArticle

Abstract

Tiqueside (CP‐88, 818, β‐tigogenin cellobioside) is an effective cholesterol absorption inhibitor that may be useful in the treatment of hypercholesteremia. We have investigated the pharmacokinetics of tiqueside in dogs, rats, rabbits, and monkeys. In dogs, the volume of distribution (Vdss) 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 bioavailability in fed dogs decreased from 6.7% for a 30 mg/kg dose to 1.7% for a 375 mg/kg dose. The oral bioavailability at a dose of 375 mg/kg was 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, Vdss 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/day was less than 0.5%. In rabbits dosed at 4.0 mg/kg iv, Vdss was 2.95 L/kg, clearance was 0.59 mL/min·kg, and half‐life was 61 h. Bioavailability for rabbits dosed in feed at 62.5 or 125 mg/kg/day was approximately 7%. Systemic exposure in rhesus monkeys after oral dosing was lower than that for dogs and rabbits. Thus, low systemic exposure to tiqueside following oral administration has been demonstrated in several animal species.

Original languageEnglish (US)
Pages (from-to)12-14
Number of pages3
JournalJournal of Pharmaceutical Sciences
Volume84
Issue number1
DOIs
StatePublished - Jan 1995

    Fingerprint

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Inskeep, P. B., Connolly, A. G., Cole, M. J., Luther, E. W., Silber, B. M., Biehl, M. L., Marzetta, C. A., & Savoy, Y. E. (1995). Pharmacokinetics of tiqueside (β‐tigogenin cellobioside) in dogs, rats, rabbits, and monkeys. Journal of Pharmaceutical Sciences, 84(1), 12-14. https://doi.org/10.1002/jps.2600840105