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
.