View Item 

Show simple item record

Using l‐Carnitine as a Pharmacologic Probe of the Interpatient and Metabolic Variability of Sepsis
dc.contributor.authorJennaro, Theodore S.
dc.contributor.authorPuskarich, Michael A.
dc.contributor.authorMcCann, Marc R.
dc.contributor.authorGillies, Christopher E.
dc.contributor.authorPai, Manjunath P.
dc.contributor.authorKarnovsky, Alla
dc.contributor.authorEvans, Charles R.
dc.contributor.authorJones, Alan E.
dc.contributor.authorStringer, Kathleen A.
dc.date.accessioned2020-10-01T23:30:43Z
dc.date.availableWITHHELD_12_MONTHS
dc.date.available2020-10-01T23:30:43Z
dc.date.issued2020-09
dc.identifier.citationJennaro, Theodore S.; Puskarich, Michael A.; McCann, Marc R.; Gillies, Christopher E.; Pai, Manjunath P.; Karnovsky, Alla; Evans, Charles R.; Jones, Alan E.; Stringer, Kathleen A. (2020). "Using l‐Carnitine as a Pharmacologic Probe of the Interpatient and Metabolic Variability of Sepsis." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 40(9): 913-923.
dc.identifier.issn0277-0008
dc.identifier.issn1875-9114
dc.identifier.urihttps://hdl.handle.net/2027.42/162752
dc.publisherWiley Periodicals, Inc.
dc.subject.otherseptic shock
dc.subject.otherpharmacometabolomics
dc.subject.othersystems pharmacology
dc.subject.othercritical care
dc.titleUsing l‐Carnitine as a Pharmacologic Probe of the Interpatient and Metabolic Variability of Sepsis
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelPharmacy and Pharmacology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/162752/2/phar2448_am.pdfen_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/162752/1/phar2448.pdfen_US
dc.identifier.doi10.1002/phar.2448
dc.identifier.sourcePharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
dc.identifier.citedreferenceLiu F, Rainosek SW, Sadovova N, et al. Protective effect of acetyl‐L‐carnitine on propofol‐induced toxicity in embryonic neural stem cells. Neurotoxicology 2014; 49 – 57.
dc.identifier.citedreferenceSherry ST, Ward MH, Kholodov M, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 2001; 1: 308 – 11.
dc.identifier.citedreferenceConsortium GT. The Genotype‐Tissue Expression (GTEx) project. Nat Genet 2013; 6: 580 – 85.
dc.identifier.citedreferenceVanham D, Spinewine A, Hantson P, Wittebole X, Wouters D, Sneyers B. Drug‐drug interactions in the intensive care unit: Do they really matter? J Crit Care 2017; 97 – 103.
dc.identifier.citedreferencePapadopoulos J, Smithburger PL. Common drug interactions leading to adverse drug events in the intensive care unit: management and pharmacokinetic considerations. Crit Care Med 2010; 6 ( Suppl ): S126 – 35.
dc.identifier.citedreferenceMarcath LA, Coe TD, Hoylman EK, Redman BG, Hertz DL. Prevalence of drug‐drug interactions in oncology patients enrolled on National Clinical Trials Network oncology clinical trials. BMC Cancer 2018; 1: 1155 – 55.
dc.identifier.citedreferencePochini L, Scalise M, Galluccio M, Indiveri C. OCTN cation transporters in health and disease: role as drug targets and assay development. J Biomol Screen 2013; 8: 851 – 67.
dc.identifier.citedreferenceGanapathy ME, Huang W, Rajan DP, et al. β‐Lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem 2000; 3: 1699 – 707.
dc.identifier.citedreferenceHirano T, Yasuda S, Osaka Y, Kobayashi M, Itagaki S, Iseki K. Mechanism of the inhibitory effect of zwitterionic drugs (levofloxacin and grepafloxacin) on carnitine transporter (OCTN2) in Caco‐2 cells. Biochem Biophys Acta 2006; 11: 1743 – 50.
dc.identifier.citedreferenceNies AT, Hofmann U, Resch C, Schaeffeler E, Rius M, Schwab M. Proton pump inhibitors inhibit metformin uptake by organic cation transporters (OCTs). PLoS One 2011; 7: e22163.
dc.identifier.citedreferenceMirrakhimov AE, Voore P, Halytskyy O, Khan M, Ali AM. Propofol infusion syndrome in adults: a clinical update. Crit Care Res Pract 2015; 260385 – 85.
dc.identifier.citedreferenceMoriyama T, Kiyonaga N, Ushikai M, Kawaguchi H, Horiuchi M, Kanmura Y. Effects of L‐carnitine on propofol‐induced inhibition of free fatty acid metabolism in fasted rats and in vitro. Open J Anesthesiol 2018; 8: 147 – 58.
dc.identifier.citedreferenceSerkova NJ, Standiford TJ, Stringer KA. The emerging field of quantitative blood metabolomics for biomarker discovery in critical illnesses. Am J Respir Crit Care Med 2011; 6: 647 – 55.
dc.identifier.citedreferenceEvans CR, Karnovsky A, Puskarich MA, Michailidis G, Jones AE, Stringer KA. Untargeted metabolomics differentiates l‐carnitine treated septic shock 1‐year survivors and nonsurvivors. J Proteome Res 2019; 5: 2004 – 11.
dc.identifier.citedreferenceChughtai K, Song Y, Zhang P, et al. Analytic morphomics: a novel CT imaging approach to quantify adipose tissue and muscle composition in allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2016; 3: 446 – 50.
dc.identifier.citedreferenceWang S, Liu X, Chen Q, Liu C, Huang C, Fang X. The role of increased body mass index in outcomes of sepsis: a systematic review and meta‐analysis. BMC Anesthesiol 2017; 1: 118.
dc.identifier.citedreferencePepper DJ, Sun J, Welsh J, Cui X, Suffredini AF, Eichacker PQ. Increased body mass index and adjusted mortality in ICU patients with sepsis or septic shock: a systematic review and meta‐analysis. Critical Care (London, England) 2016; 1: 181.
dc.identifier.citedreferenceNg PY, Eikermann M. The obesity conundrum in sepsis. BMC Anesthesiol 2017; 1: 147 – 47.
dc.identifier.citedreferenceMofarrahi M, Sigala I, Guo Y, et al. Autophagy and skeletal muscles in sepsis. PLoS One 2012; 10: e47265.
dc.identifier.citedreferenceLucidi C, Lattanzi B, Di Gregorio V, et al. A low muscle mass increases mortality in compensated cirrhotic patients with sepsis. Liver Int 2018; 5: 851 – 57.
dc.identifier.citedreferenceLee Y, Park HK, Kim WY, Kim MC, Jung W, Ko BS. Muscle mass depletion associated with poor outcome of sepsis in the emergency department. Ann Nutr Metab 2018; 4: 336 – 44.
dc.identifier.citedreferenceDe Paepe P, Belpaire FM, Buylaert WA. Pharmacokinetic and pharmacodynamic considerations when treating patients with sepsis and septic shock. Clin Pharmacokinet 2002; 14: 1135 – 51.
dc.identifier.citedreferenceRebouche CJ. Kinetics, pharmacokinetics, and regulation of L‐carnitine and acetyl‐L‐carnitine metabolism. Ann New York Acad Sci 2004; 1033: 30 – 41.
dc.identifier.citedreferenceKoyner JL. Assessment and diagnosis of renal dysfunction in the ICU. Chest 2012; 6: 1584 – 94.
dc.identifier.citedreferenceCrass RL, Pai MP. Estimating renal function in drug development: time to take the fork in the road. J Clin Pharmacol 2019; 2: 159 – 67.
dc.identifier.citedreferenceChung KP, Chen GY, Chuang TY, et al. Increased plasma acetylcarnitine in sepsis is associated with multiple organ dysfunction and mortality: a multicenter cohort study. Crit Care Med 2019; 2: 210 – 18.
dc.identifier.citedreferenceSinger M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis‐3). JAMA 2016; 8: 801 – 10.
dc.identifier.citedreferenceRudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet 2020; 10219: 200 – 11.
dc.identifier.citedreferenceSeymour CW, Kennedy JN, Wang S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA 2019; 20: 2003 – 17.
dc.identifier.citedreferenceCohen J, Vincent JL, Adhikari NK, et al. Sepsis: a roadmap for future research. Lancet Infect Dis 2015; 5: 581 – 614.
dc.identifier.citedreferencePravda J. Metabolic theory of septic shock. World J Crit Care Med 2014; 2: 45 – 54.
dc.identifier.citedreferenceLiu Z, Triba MN, Amathieu R, et al. Nuclear magnetic resonance‐based serum metabolomic analysis reveals different disease evolution profiles between septic shock survivors and non‐survivors. Crit Care 2019; 1: 169.
dc.identifier.citedreferenceJansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate‐guided therapy in intensive care unit patients: a multicenter, open‐label, randomized controlled trial. Am J Respir Crit Care Med 2010; 6: 752 – 61.
dc.identifier.citedreferenceJones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 2010; 8: 739 – 46.
dc.identifier.citedreferenceHernández G, Ospina‐Tascón GA, Damiani LP, et al. Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28‐day mortality among patients with septic shock: the ANDROMEDA‐SHOCK randomized clinical trial. JAMA 2019; 7: 654 – 64.
dc.identifier.citedreferenceLevy B, Gibot S, Franck P, Cravoisy A, Bollaert PE. Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet (London, England) 2005; 9462: 871 – 5.
dc.identifier.citedreferenceReuter SE, Evans AM. Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects. Clin Pharmacokinet 2012; 9: 553 – 72.
dc.identifier.citedreferenceSharma S, Black SM. Carnitine homeostasis, mitochondrial function, and cardiovascular disease. Drug Discov Today Dis Mech 2009; 1–4: e31 – e39.
dc.identifier.citedreferenceSemba RD, Trehan I, Li X, et al. Environmental enteric dysfunction is associated with carnitine deficiency and altered fatty acid oxidation. EBioMedicine 2017; 17: 57 – 66.
dc.identifier.citedreferenceSinger M. The role of mitochondrial dysfunction in sepsis‐induced multi‐organ failure. Virulence 2014; 1: 66 – 72.
dc.identifier.citedreferenceProtti A, Fortunato F, Artoni A, et al. Platelet mitochondrial dysfunction in critically ill patients: comparison between sepsis and cardiogenic shock. Critical care (London, England) 2015; 19: 39.
dc.identifier.citedreferenceLangley RJ, Tsalik EL, van Velkinburgh JC, et al. An integrated clinico‐metabolomic model improves prediction of death in sepsis. Sci Transl Med 2013; 5: 195ra95.
dc.identifier.citedreferenceJohansson PI, Nakahira K, Rogers AJ, et al. Plasma mitochondrial DNA and metabolomic alterations in severe critical illness. Critical care (London, England) 2018; 22: 360.
dc.identifier.citedreferenceEaton S, Fukumoto K, Stefanutti G, Spitz L, Zammit VA, Pierro A. Myocardial carnitine palmitoyltransferase I as a target for oxidative modification in inflammation and sepsis. Biochem Soc Trans 2003; 31: 1133 – 36.
dc.identifier.citedreferenceVary TC. Sepsis‐induced alterations in pyruvate dehydrogenase complex activity in rat skeletal muscle: effects on plasma lactate. Shock (Augusta, GA) 1996; 2: 89 – 94.
dc.identifier.citedreferenceGasparetto A, Corbucci GG, De Blasi RA, et al. Influence of acetyl‐L‐carnitine infusion on haemodynamic parameters and survival of circulatory‐shock patients. Int J Clin Pharmacol Res 1991; 2: 83 – 92.
dc.identifier.citedreferenceCorbucci GG, Loche F. L‐carnitine in cardiogenic shock therapy: pharmacodynamic aspects and clinical data. Int J Clin Pharmacol Res 1993; 2: 87 – 91.
dc.identifier.citedreferenceCorbucci GG, Lettieri B. Cardiogenic shock and L‐carnitine: clinical data and therapeutic perspectives. Int J Clin Pharmacol Res 1991; 6: 283 – 93.
dc.identifier.citedreferencePuskarich MA, Kline JA, Krabill V, Claremont H, Jones AE. Preliminary safety and efficacy of L‐carnitine infusion for the treatment of vasopressor‐dependent septic shock: a randomized control trial. J Parenter Enteral Nutr 2014; 6: 736 – 43.
dc.identifier.citedreferenceJones AE, Puskarich MA, Shapiro NI, et al. Effect of levocarnitine vs placebo as an adjunctive treatment for septic shock: the rapid administration of carnitine in sepsis (RACE) randomized clinical TrialEffect of levocarnitine vs placebo as an adjunctive treatment for septic shockeffect of levocarnitine vs placebo as an adjunctive treatment for septic shock. JAMA Network Open 2018; 8: e186076 – e76.
dc.identifier.citedreferencePuskarich MA, Evans CR, Karnovsky A, Das AK, Jones AE, Stringer KA. Septic shock nonsurvivors have persistently elevated acylcarnitines following carnitine supplementation. Shock (Augusta, Ga) 2018; 4: 412 – 19.
dc.identifier.citedreferencePuskarich MA, Finkel MA, Karnovsky A, et al. Pharmacometabolomics of l‐carnitine treatment response phenotypes in patients with septic shock. Ann Am Thorac Soc 2015; 1: 46 – 56.
dc.identifier.citedreferenceStorey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci USA 2003; 16: 9440 – 45.
dc.identifier.citedreferenceMacKenzie M, Hall R. Pharmacogenomics and pharmacogenetics for the intensive care unit: a narrative review. Can J Anaesth 2017; 1: 45 – 64.
dc.identifier.citedreferenceVincent J‐L. The coming era of precision medicine for intensive care. Critical care (London, England) 2017; 21: 314 – 14.
dc.identifier.citedreferenceMagoulas PL, El‐Hattab AW. Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management. Orphanet journal of rare diseases 2012; 7: 68.
dc.identifier.citedreferenceUrban TJ, Gallagher RC, Brown C, et al. Functional genetic diversity in the high‐affinity carnitine transporter OCTN2 (SLC22A5). Mol Pharmacol 2006; 5: 1602 – 11.
dc.identifier.citedreferenceTahara H, Yee SW, Urban TJ, et al. Functional genetic variation in the basal promoter of the organic cation/carnitine transporters OCTN1 (SLC22A4) and OCTN2 (SLC22A5). J Pharmacol Exp Therap 2009; 1: 262 – 71.
dc.identifier.citedreferenceGrube M, Meyer zu Schwabedissen HEU, Präger D, et al. Uptake of cardiovascular drugs into the human heart: expression, regulation, and function of the carnitine transporter OCTN2 (SLC22A5). Circulation 2006; 8: 1114 – 22.
dc.owningcollnameInterdisciplinary and Peer-Reviewed


Files in this item

Name:
phar2448.pdf
Size:
415.5KB
Format:
PDF
View/Open
Name:
phar2448_am.pdf
Size:
396.7KB
Format:
PDF
View/Open

Show simple item record

Remediation of Harmful Language

The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.

Accessibility

If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.