Inhibitory effect of docosahexaenoic acid (DHA) on the intestinal metabolism of midazolam: In vitro and in vivo studies in rats

Fatty Acid Binding Proteins: Potential Chaperones of Cytosolic Drug Transport in the Enterocyte?

“…The major products of gut wall metabolism of midazolam are 4-hydroxy midazolam and 1-hydroxy midazolam, and there is conflicting evidence to suggest whether 4-hydroxy or 1-hydroxy midazolam is the major intestinal metabolite (29,30,56,57). In the current study, levels of the 4-hydroxy-metabolite were used to indicate the extent of metabolism.…”

“…Midazolam was also chosen, as it is subject to significant first-pass metabolism in the enterocyte (29,30) and therefore offered the opportunity to probe the impact of FABP binding on intracellular drug metabolism. Ibuprofen (31) is not significantly metabolised during intestinal perfusion.…”

“…The extraction ratio was calculated at the conclusion of experiments as described previously (29,30,34), from the ratio of the sum of the mass of metabolite in the perfusate (which in all cases was zero as no metabolite was detected in perfusate), blood and intestinal tissue to the sum of the mass of both metabolite in the perfusate, blood and intestinal tissue and parent drug in the intestinal tissue and blood, as shown in Eq. 4 below.…”

Protective Effect of Docosahexaenoic Acid Against Cyclosporine A-Induced Nephrotoxicity in Rats: A Possible Mechanism of Action

“…One of the two groups was fed orally with DHA at a dose of 100 mg/kg of body weight for 4 days before and for 21 days concomitant with CsA. 16,11 The third group received DHA alone in the same dose and by the same route of administration for 25 consecutive days. The last group of animals served as control and received by gavage an equivalent volume of vehicle for the same number of days.…”

“…[12][13][14][15] Docosahexaenoic acid (22:6, n-3; DHA) is an essential polyunsaturated fatty acid, which is predominant in fish and marine oils. 16 Polyunsaturated fatty acids are known to have potential cardiovascular benefits that include lowering blood pressure and improving vascular tone, whereas their impact on lipid peroxidation has been controversial. [17][18][19][20][21] In view of this, we investigated the ability of DHA to restore the deteriorated renal functions induced by CsA in a rat model.…”