Effect of succinic acid and tween-80 on glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine.
We studied the effect of succinic acid on the process of glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine after peroral and intraperitoneal administration in the form of succinate or a base. Since the basic form of 2-ethyl-6-methyl-3-hydroxypyridine is insoluble in water, it was administered in 5% Tween-80. It was necessary to evaluate also the effect of Tween-80 on glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine in different administration routes. Quantitative assay of glucuronidated fractions was performed by the method of reversed-phase HPLC with fluorometrical detection. The detection limit for this method was 10 ng/ml. We confirmed that the major excretion pathway for 2-ethyl-6-methyl-3-hydroxypyridine is conjugation with glucuronic acid. It was found that succinic acid increased excretion of glucuronidated metabolite after both peroral and intraperitoneal administration of 2-ethyl-6-methyl-3-hydroxypyridine in the form of succinate and base in 5% Tween-80. The effect of Tween-80 was detected only after peroral administration, which was probably related to its effect on absorption of this compound. Tween-80 increased excretion of glucuronate after peroral administration of 2-ethyl-6-methyl-3-hydroxypyridine in the form of succinate and in 5% Tween solution.
Baranov
P A
PA
V. V. Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Russia. baranov@dopingcontrol.ru
Kravtsova
O U
OU
Sariev
A K
AK
Sherdev
V P
VP
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D020723:Glucuronic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D010847:Picolines / Q000378:metabolism*; D011136:Polysorbates / Q000008:administration & dosage / Q000378:metabolism*; D011897:Random Allocation; D019802:Succinic Acid / Q000008:administration & dosage / Q000378:metabolism*; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000378:metabolism*
D000975:Antioxidants; D010847:Picolines; D011136:Polysorbates; D013501:Surface-Active Agents; D020723:Glucuronic Acid; D019802:Succinic Acid; C009820:6-methyl-2-ethyl-3-hydroxypyridine