Physiologic and metabolic influences on enterohepatic recirculation: Simulations based upon the disposition of valproic acid in the rat
Journal of Pharmacokinetics and Biopharmaceutics, ISSN: 0090-466X, Vol: 19, Issue: 2, Page: 189-225
1991
- 38Citations
- 235Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations38
- Citation Indexes38
- 38
- CrossRef25
- Captures235
- Readers235
Article Description
The potential influence of alterations in several physiologic processes (hepatocellular egress, biliary excretion, gastrointestinal transit) and biotransformation steps (oxidative metabolism, glucuronidation) on the disposition of agents subject to significant enterohepatic recirculation (ER) via the glucuronide conjugate was examined in a series of simulation experiments. The model of ER developed was based upon the disposition of valproic acid (VPA) and valproate glucuronide (VPA-G) in the rat. The systemic disposition of VPA was simulated following changes in several processes contributing to (or competing with) ER: hepatic oxidative metabolism, hepatic glucuronidation, sinusoidal egress of glucuronide conjugate, canalicular egress of glucuronide conjugate, and gastrointestinal transit. Changes in the formation clearance of VPA-G resulted in a less than proportional change in systemic clearance of VPA, whereas changes in oxidative metabolism led to a greater than proportional change in systemic clearance. Furthermore, alterations in hepatocellular egress of VPA-G affected the disposition of the parent compound, suggesting that drug interactions or disease state effects on metabolite transport may be misinterpreted as effects at the level of metabolite formation. Analytical methods are proposed to recover the intrinsic kinetic parameters (formation clearances of metabolites, renal clearance of parent, volume of distribution) in the presence of ER from the systemic disposition of the parent alone. © 1991 Plenum Publishing Corporation.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0025891467&origin=inward; http://dx.doi.org/10.1007/bf01073869; http://www.ncbi.nlm.nih.gov/pubmed/2013839; http://link.springer.com/10.1007/BF01073869; http://link.springer.com/content/pdf/10.1007/BF01073869; https://dx.doi.org/10.1007/bf01073869; https://link.springer.com/article/10.1007/BF01073869
Springer Nature
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