Biotransformation and pharmacokinetics of inositol hexanicotinate in rats.
Article Details
- CitationCopy to clipboard
Milton SG, Robinson K, Ma J, Wei B, Poon IO, Liang D
Biotransformation and pharmacokinetics of inositol hexanicotinate in rats.
Xenobiotica. 2013 Sep;43(9):817-22. doi: 10.3109/00498254.2012.762591. Epub 2013 Jan 24.
- PubMed ID
- 23347001 [ View in PubMed]
- Abstract
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 microg/mL) was incubated in plasma at 37 degrees 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 microg/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.
