Inhibition of Glucuronidation and Oxidative Metabolism of Buprenorphine Using GRAS Compounds or Dietary Constituents/Supplements: In Vitro Proof of Concept

Abstract The present study investigated the potential of generally recognized as safe compounds or dietary substances to inhibit the presystemic metabolism of buprenorphine and increase its oral bioavailability. Using IVIVE, the buprenorphine extraction ratios in intestine and liver were predicted as 96% and 71%, respectively. In addition, the relative fraction of buprenorphine metabolized by oxidation and glucuronidation in these two organs was estimated using pooled human intestinal and liver microsomes. In both organs, oxidation appeared to be the major metabolic pathway with a six and four fold higher intrinsic clearance than glucuronidation in intestine and liver, respectively. The oral bioavailability of buprenorphine was predicted to be 1.16%. Inhibition of 75% and 50% of intestinal and hepatic presystemic metabolism would result in Foral of 49%, which is comparable to the bioavailability of sublingual buprenorphine. In human liver microsomes, chrysin, curcumin, ginger extract, hesperitin, magnolol, quercetin and silybin inhibited ≥50% glucuronidation whereas chrysin, curcumin, ginger extract, 6‐gingerol, pterostilbene, resveratrol and silybin exhibited ≥30% inhibition of oxidation. In human intestinal microsomes, curcumin, ginger extract, α‐mangostin, quercetin and silybin inhibited ≥50% glucuronidation while chrysin, ginger extract, α‐mangostin, pterostilbene and resveratrol exhibited ≥30% inhibition of oxidation. These results demonstrate the feasibi...
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: Special Issue Article Source Type: research