Pharmacokinetics, Bioavailability, and Dose Range-Finding of NSC-D629243 in Beagle Dogs (Phase 1) and Bioavailability of NSC-D62924 in Various Formulations in Beagle Dogs (Phase 2).

摘要

The pharmacokinetic profile of NSC-D629243 appeared to be significantly influenced by the vehicles used in these studies. The solubility of the test drug is low in most acceptable biological vehicles, including Liposyn II which was used in these studies. The physical interactions between the test drug and Liposyn II resulted in poor solubility of the formulated dose. Therefore, the measured concentration of the prepared dose was lower than the target concentration. The viscous character of the formulated doses also appeared to impede distribution through the vascular system following intravenously administered doses. In identifying an alternative vehicle, the drug appeared to be more readily soluble and more homogenous in sesame oil than Polyethylene glycol-300. In addition, based on plasma drug levels and bioavailability estimates, the preferred route and vehicle of administration were the oral route and sesame oil vehicle, respectively. No observed toxic effects of NSC-D629243 were evident during the in-life phases of these studies.