Biotransformation and pharmacokinetics of inositol hexanicotinate in rats.
Inositol hexanicotinate (IHN) is an ester of the anti-hyperlipidemic drug nicotinic acid (NA). This study assessed the hydrolysis rate of IHN in human and rat plasma, and pharmacokinetics of the drug using a rat animal model. IHN (10 or 50 µg/mL) was incubated in plasma at 37 °C for 72 h. Kinetic parameters were determined based on the disappearance of IHN and the appearance of NA. The mean IHN disappearance and NA appearance half-lives were 1.07 and 3.93 h in human plasma, and 0.152 and 2.68 h in rat plasma. Increasing the initial plasma concentration to 50 µg/mL increased the NA appearance half-life in human and rat plasma to 4.66 and 6.47 h, respectively. After single 50 or 100 mg/kg intravenous dose of IHN to Sprague-Dawley rats, the drug showed statistically significant dose-dependent alterations in systemic clearance, suggesting a non-linear saturable elimination of IHN. Dose-normalized mean plasma levels of NA increased by 30% with increasing IHN dose (p < 0.02). The mean metabolic ratio (i.e. NA/IHN AUC ratio) significantly increased with increasing IHN dose (p < 0.05). The results provide first indication of saturable elimination and rapid disappearance of IHN, while niacin was slowly formed.
Department of Pharmaceutical Sciences, Texas Southern University, Houston, TX 77004, USA.
Shirlette G
SG
Milton
Keila
K
Robinson
Jing
J
Ma
Bo
B
Wei
Ivy O
IO
Poon
Dong
D
Liang
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008297:Male; D009539:Nicotinic Acids / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009539:Nicotinic Acids; C005193:Inositol Niacinate