Dose-dependent cholesterol-lowering effects of D-003 on normocholesterolemic rabbits

Objectives: The goal of the present study was to evaluate the effects of D- 003 (5 to 200 mg/kg) administered orally for 30 days on the serum lipid pro file of normocholesterolemic New Zealand rabbits as well as the effects of treatment withdrawal for the following 30 days. Background: D-003 is a mixture of higher primary aliphatic acids; octacosan oic acid is its major component. Methods: Thirty-five animals were adapted to experimental conditions for 15 days and then randomized to 5 study groups: a control group, which receive d only orally equivalent volumes of the vehicle, and 4 groups treated with the various doses of D-003 (5, 25, 100, or 200 mg/kg). Results: After 30 days of treatment, D-003 significantly (P < 0.01) and dos e-dependently reduced levels of both total cholesterol (TC) (range, 27.5% t o 37.3%) and low-density lipoprotein cholesterol (LDL-C) (range, 64.5% to 8 4.4%). After 30 days of treatment, high-density lipoprotein cholesterol (HD L-C) levels increased in all treated groups compared with baseline. Only th e final values of the groups receiving doses of 25 to 200 mg/kg mere signif icantly larger (P < 0.01) than those of the control group. This effect was not dose dependent. No drug-related effects on triglycerides mere noted. Th ere mere no significant changes in the control group's lipid profile during the study. The effects of D-003 on TC, LDL-C, and HDL-C levels were revers ible after the washout period, with complete recovery to baseline values af ter 30 days of treatment withdrawal. No rebound effects were observed. In a ddition, drug-related toxicity regarding mortality, food consumption, weigh t gain, or blood chemistry safety indicators was not evident. Conclusions: Results of this study suggest that D-003 has reversible choles terol-lowering effects characterized by a dose-dependent reduction of TC an d LDL-C values accompanied by a non-dose-dependent increase in HDL-C levels .