Cytochrome P450 mediated-drug metabolism is reduced in children with sepsis-induced multiple organ failure

Carcillo, Joseph A.; Doughty, Lesley; Kofos, Danny; Frye, Reginald F.; Kaplan, Sandra S.; Sasser, Howell; Burckart, Gilbert J.
June 2003
Intensive Care Medicine;Jun2003, Vol. 29 Issue 6, p980
Academic Journal
journal article
Objective: Antipyrine metabolism is a "gold standard" measure of mixed cytochrome P450 (CYP) mediated drug metabolism in humans. Cytokines (e.g., interleukin-6) and nitric oxide reduce CYP 450 activity in vitro and in vivo. Because interleukin-6 and nitric oxide production increases in children with sepsis-induced multiple organ failure, we hypothesized impaired CYP 450 mediated drug metabolism in this population.Methods: Fifty-one consecutive children with sepsis and six critically ill children without sepsis were enrolled and given 18 mg/kg antipyrine per NG. Plasma antipyrine elimination rate, elimination half-life, and apparent oral clearance were measured and calculated. Plasma interleukin-6 and nitrite plus nitrate levels were measured and organs failing scored on days 1-3 of sepsis.Results: Children with sepsis had a twofold reduction in antipyrine clearance. Children with persistent failure of three or more organs had a fourfold reduction in antipyrine clearance. Antipyrine clearance was inversely correlated to circulating interleukin-6 and nitrite plus nitrate levels and to number of organ failures.Conclusions: Interpretation CYP 450 mediated drug metabolism is decreased in children with sepsis, related in part to the degree of inflammation and organ failure. For drugs metabolized by CYP 450 enzymes there is an urgent need to reevaluate the use of standard drug dosage schedules in the sepsis population


Related Articles

  • Manifold beneficial effects of acetyl salicylic acid and nonsteroidal anti-inflammatory drugs on sepsis. Eisen, Damon // Intensive Care Medicine;Aug2012, Vol. 38 Issue 8, p1249 

    Introduction: Acetyl salicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) may have potential as adjunctive agents for sepsis. Materials: This review considers the large body of literature that indicates a basis for sepsis therapy with ASA and suggests an agenda for future...

  • Naproxen.  // Reactions Weekly;5/20/2006, Issue 1102, p11 

    Discusses research on enhanced production of interleukin-6 in vitro by non-steroidal anti-inflammatory drug in a child of systemic juvenile idiopathic arthritis with naproxen-triggered microphase activation syndrome. Reference to a study by T. Ando and colleagues, presented at the Annual...

  • What to Use for Acute Gout—NSAIDs or Steroids? Scherger, Joseph E. // Internal Medicine Alert;9/29/2008, Vol. 30 Issue 18, p137 

    The article presents an abstract and a commentary on the article "What to Use for Acute Gout― NSAIDs or Steroids," by Joseph E. Scherger.

  • Efeito da dexametasona e do cetoprofeno na osteogênese e na resistência óssea em ratos. dos Santos da Silva, Patrícia Costa; Camilli, José Ângelo; Nakagaki, Wilson Romero; Soares, Evelise Aline; Dias Garcia, José Antonio // Revista de Ciências Farmacêuticas Básica e Aplicada;2012, Vol. 33 Issue 2, p217 

    This study aimed at evaluating the effect of ketoprofen (NSAID) and dexamethasone (SAID) on osteogenesis around a dense hydroxyapatite (DHA) implant in the tibia and parietal bone, and on the bone resistance. Fifteen fifty-day-old Wistar rats weighing on average 250±30 g were used. The...

  • Hospitalization for Severe Bacterial Infections in Children after Exposure to NSAIDs. Leroy, Sandrine; Marc, Elisabeth; Bavoux, Françoise; Tréluyer, Jean-Marc; Gendrel, Dominique; Bréart, Gérard; Pons, Gérard; Chalumeau, Martin // Clinical Drug Investigation;2010, Vol. 30 Issue 3, p179 

    Background: NSAIDs are widely used to treat fever and pain in children, but their possible role in the progression of some bacterial infections is controversial. Objective: This study was performed to analyse reported cases of severe bacterial infection associated with NSAID exposure in children...

  • MUSCULOSKELETAL DISORDERS.  // Monthly Prescribing Reference;Dec2011, Vol. 27 Issue 12, p237 

    The article offers information on several drugs prescribed for musculoskeletal disorders. The interleukin-6 receptor inhibitor Actempra from Genentech is used to treat rheumatoid arthritis and systemic juvenile idiopathic arthritis. Recommended dosages of non-steroidal anti-inflammatory drug...

  • Treatment of refractory adult-onset still's disease with tocilizumab: report of two cases and review of the literature. Thonhofer, Rene; Hiller, Manuela; Just, Horst; Trummer, Markus; Siegel, Cornelia; Dejaco, Christian // Rheumatology International;Dec2011, Vol. 31 Issue 12, p1653 

    Adult-onset Still's disease (AOSD) is empirically treated with nonsteroidal anti-inflammatory drugs, corticosteroids, conventional disease-modifying antirheumatic drugs, tumor necrosis factor-blocking agents or anakinra. The monoclonal anti-interleukin (IL)-6 antibody tocilicumab (TOC) has...

  • Tocilizumab for the treatment of adult-onset Still's disease: results from a case series. Cipriani, Paola; Ruscitti, Piero; Carubbi, Francesco; Pantano, Ilenia; Liakouli, Vasiliki; Berardicurti, Onorina; Giacomelli, Roberto // Clinical Rheumatology;Jan2014, Vol. 33 Issue 1, p49 

    Adult-onset Still's disease (AOSD) is a chronic inflammatory disease of unknown etiology which commonly affects young adults. Treatment of AOSD patients includes nonsteroidal anti-inflammatory drugs, corticosteroids, and DMARDs. Interleukin (IL)-6 blockade is an attractive therapeutic option for...

  • Experiences with chest trauma: Where do we stand today. Mohta, M.; Kumar, P.; Mohta, A.; Bhardwaj, R.; Tyagi, A.; Sethi, A. K. // Indian Journal of Critical Care Medicine;Jan-Mar2006, Vol. 10 Issue 1, p25 

    Background and Aims: Chest trauma is a major public health problem in India, but only few studies have been conducted to analyze its magnitude and management. The present study was carried out to determine the epidemiological profile of chest trauma cases and to analyze the management strategies...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics