Inhibition of hepatic gluconeogenesis by niflumic acid correlates with the concentration of the free form.
Inhibition of hepatic gluconeogenesis by niflumic acid, a non-steroidal antiinflammatory drug, was measured in order to correlate the effect of the drug with the concentration of the free drug. The concentration of free drug was changed in two ways: (a) by changing the albumin concentration at a fixed total (free+bound) niflumic acid concentration; and, (b) by changing the drug concentration at a fixed albumin concentration. The degree of inhibition of gluconeogenesis by niflumic acid depends strictly on the concentration of the free drug, with half-maximal inhibition at 19.25 microM. This result is consistent with binding equilibrium in the extracellular space and with a flow-limited distribution between the extra- and intracellular spaces as proposed by our previous work.
Kelmer-Bracht
A M
AM
Department of Biochemistry, University of Maringá, Brazil.
Bracht
A
A
D000818:Animals; D001682:Biological Availability; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000037:antagonists & inhibitors*; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009544:Niflumic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D010101:Oxygen Consumption; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000494:pharmacology
D007773:Lactates; D011773:Pyruvates; D012709:Serum Albumin; D019344:Lactic Acid; D009544:Niflumic Acid; D019289:Pyruvic Acid; D005947:Glucose