Preclinical Pharmacodynamic and Pharmacokinetic Studies of Investigational New Drugs
Abstract
The occurrence of clinical signs of toxicity and observable effects on and around the injection site following iv injection for 7 days of a single, daily dose of an artelinic acid/lysine (AL/lysine) formulation, equal to or greater than the anticipated clinical dose, was investigated in Beagle dogs. Groups consisting of one or two male and one or two female dogs were given an iv dose of 2 or 4 mL of an AL/lysine formulation containing 0, 10, or 30 mg/mL of artelinic acid daily for 7 days. All doses were delivered into a peripheral leg vein over an approximate 10-minute interval, using an infusion pump. On Days 1-14, each dog was observed at least twice daily for signs of clinical toxicity and the site of injection was closely examined for irritation/swelling or other adverse reactions. No clinical signs of toxicity or adverse reactions at the injection site were observed for any dogs given the vehicle control formulation (either 2 mL or 4 mL), or for dogs given 2 mL of either the 10 or 30 mg/mL AL/lysine formulation, or for the male dogs given 4 mL of the 30 mg/mL AL/lysine formulation. The two female dogs given 4 mL of 30 mg/mL AL/lysine displayed transient swelling in the leg, near the injection site, beginning on Day 5 or 6 of dosing and continuing through Day 10 or 11; no necrosis, discoloration, or other adverse signs were evident in these two animals. The results of this study indicated that an injectable formulation of artelinic acid/lysine was well tolerated by dogs given a single iv dose for 7 consecutive days. In future work, the pharmacodynamic effects of iv administered antelinic acid and artesunic acid, as assessed by signs of clinical and pathological toxicity, will be investigated in rats.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA396457
Entities
People
- Patricia E. Noker
Organizations
- Southern Research