Reports Summarize Pharmacokinetics Findings from Bristol-Myers Squibb (Metabolite Kinetics: The Segregated Flow Model for Intestinal and Whole Body Physiologically Based Pharmacokinetic Modeling to Describe Intestinal and Hepatic ...)
By a News Reporter-Staff News Editor at Drug Week -- Research findings on Pharmacokinetics are discussed in a new report. According to news reporting originating from Princeton, New Jersey, by NewsRx correspondents, research stated, "We used the intestinal segregated flow model (SFM) versus the traditional model ™, nested within physiologically based pharmacokinetic (PBPK) models, to describe the biliary and urinary excretion of morphine 3 beta-glucuronide (MG) after intravenous and intraduodenal dosing of morphine in rats in vivo. The SFM model describes a partial (5%-30%) intestinal blood flow perfusing the transporter- and enzyme-rich enterocyte region, whereas the TM describes 100% flow perfusing the intestine as a whole."
Our news editors obtained a quote from the research from Bristol-Myers Squibb, "For the SFM, drugs entering from the circulation are expected to be metabolized to lesser extents by the intestine due to the segregated flow, reflecting the phenomenon of shunting and route-dependent intestinal metabolism. The poor permeability of MG crossing the liver or intestinal basolateral membranes mandates that most of MG that is excreted into bile is hepatically formed, whereas MG that is excreted into urine originates from both intestine and liver metabolism, since MG is effluxed back to blood. The ratio of MG amounts in urine/bile (A(urine)(MG)/A(bile)(MG)) for intraduodenal/intravenous dosing is expected to exceed unity for the SFM but approximates unity for the TM. Compartmental analysis of morphine and MG data, without consideration of the permeability of MG and where MG is formed, suggests the ratio to be 1 and failed to describe the kinetics of MG. Theobserved intraduodenal/intravenous ratio of A(urine),(MG)(4h)/A(bile,4h)(MG)(2.55 at 4 hours) was better predicted by the SFM-PBPK (2.59 at 4 hours) and not the TM-PBPK (1.0), supporting the view that the SFM is superior for the description of intestinal-livermetabolism of morphine to MG."
According to the news editors, the research concluded: "The SFM-PBPK model predicts an appreciable contribution of the intestine to first pass M metabolism."
For more information on this research see: Metabolite Kinetics: The Segregated Flow Model for Intestinal and Whole Body Physiologically Based Pharmacokinetic Modeling to Describe Intestinal and Hepatic Glucuronidation of Morphine in Rats In Vivo. Drug Metabolism and Disposition, 2016;44(7):1123-1138. Drug Metabolism and Disposition can be contacted at: Amer Soc Pharmacology Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20814-3995, USA (see also Pharmacokinetics).
The news editors report that additional information may be obtained by contacting Q.J. Yang, Bristol Myers Squibb Co, Princeton, NJ, United States. Additional authors for this research include J.H. Fan, S. Chen, L.T. Liu, H.D. Sun and K.S. Pang.
Keywords for this news article include: Princeton, New Jersey, United States, North and Central America, Pharmacokinetics, Pharmaceuticals, Therapy, Drugs, Bristol-Myers Squibb.
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