Effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid in rats.

Abstract

Pyridoxine is always simultaneously administered orally with isoniazid for tuberculosis patients in the clinic to prevent or treat the nervous system side effects induced by isoniazid. So the aim of this research was to investigate the effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid. The intestinal absorption of isoniazid with or without pyridoxine was investigated by the rat single-pass intestinal perfusion model in situ, and a high-performance liquid chromatographic method was applied to study the pharmacokinetics of isoniazid with or without pyridoxine. The results suggested that the intestinal apparent permeability (P app) and intestinal absorption rate constant (K a) for isoniazid (30 μg/ml) were decreased by 43.7 and 36.4 %, respectively, by co-perfused pyridoxine (40 μg/ml). In vivo, the effect of pyridoxine on isoniazid pharmacokinetic correlated with the doses of pyridoxine. The blood concentrations of isoniazid at the absorption phase were affected by co-administered pyridoxine, but the AUC and C max of isoniazid were not greatly affected by pyridoxine as expected from the inhibition by pyridoxine of the intestinal absorption of isoniazid, which could be caused by its rapid absorption phase. Therefore, although the intestinal absorption of isoniazid could be significantly inhibited by pyridoxine, the pharmacokinetics of isoniazid oral administration was not greatly affected by the decreased intestinal absorption of isoniazid due to its rapid absorption.

• Authors: Yan Zhou, Yang Jiao, Yu-Hui Wei, Guo-Rong Zhang, Jian-Ping Zhang, Jiang-Xia Ren, Fan Zhang, Guo-Qiang Zhang, Hao-Gang Duan, Xin-An Wu
• Journal: European journal of drug metabolism and pharmacokinetics (Eur J Drug Metab Pharmacokinet) Vol. 38 Issue 1 Pg. 5-13 (Mar 2013) ISSN: 0378-7966 [Print] France
• PMID: 23090666 (Publication Type: Journal Article)

Chemical References

• Antitubercular Agents
• Vitamin B Complex
• Pyridoxine
• Isoniazid

Topics

• Administration, Oral
• Animals
• Antitubercular Agents (administration & dosage, blood, pharmacokinetics)
• Area Under Curve
• Chromatography, High Pressure Liquid
• Drug Interactions
• Half-Life
• Intestinal Absorption (drug effects)
• Intestinal Mucosa (metabolism)
• Intestines (drug effects)
• Isoniazid (administration & dosage, blood, pharmacokinetics)
• Male
• Metabolic Clearance Rate
• Perfusion
• Permeability
• Pyridoxine (pharmacology)
• Rats
• Rats, Wistar
• Vitamin B Complex (pharmacology)