Adjunct Professor of Medicine, Indiana University School of Medicine
PharmD, University of California, San Francisco, 1975
Diplomate, American Board of Clinical Pharmacology, 1995
We are currently investigating the effects of parental nutrition on hepatic drug metabolism. TPN, by bypassing the intestine, alters several physiological variables including hepatic drug metabolizing capacity and the age-related response to this perturbation remains to be explored. Many hospitalized elderly receive inadequate nutrition in part because TPN is a life-sustaining technology and decisions regarding its initiation or withdrawal are highly controversial. TPN is expensive, whether used at home or in an institutionalized setting. It has been estimated that one in six elderly lives in poverty, thus a major factor influencing nutrition in the elderly is poverty. Finally, catheter sepsis, venous thrombosis and better fluid and electrolyte management continue to present challenges to the use of TPN. Developing strategies and collecting data for the safe and effective use of drugs in the population of hospitalized elderly patients, who increasingly require nutritional intervention, is therefore critical. This research has recently established a chronically catheterized rat model for studying the effects of TPN on drug metabolism and has shown that drug conjugation is markedly decreased in rats receiving a continuous TPN infusion of dextrose and amino acids for 10-14 days, compared to the same animals allowed to eat rat chow. In vivo, drug conjugation is assessed by characterizing the pharmacokinetics of acetaminophen elimination and the individual processes principally responsible for elimination, the formation of acetaminophen sulfate and acetaminophen glucuronide. These studies indicate that bypassing the intestine appears to be the key factor regulating hepatic conjugative metabolism.
Desta Z, Metzger IF, Thong N, Lu JBL, Callaghan TJ, Skaar RC, Flockhart DA and Galinsky RE. Inhibition of CYP2B6 activity by voriconazole profiled using efavirenz disposition in healthy volunteers Antimicrob Agents and Chemother 60:6813-6822, 2016, doi:10.1128/AAC.01000-16
Galinsky, R.E. and Svensson, C.K. "Basic Pharmacokinetics and Pharmacodynamics." Remington: The Science and Practice of Pharmacy, 21st Edition. Philadelphia: Lippincott Williams & Wilkins, 2006. 1171-1190.