Cytochrome P450 3A4 activity after surgical stress

Haas, Curtis E.; Kaufman, David; Jones, Carolyn E.; Burstein, Aaron H.; Reiss, William

doi:10.1097/01.ccm.0000063040.24541.49

Cited by 81 publications

(61 citation statements)

References 55 publications

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“…Therefore, the lower concentration part (1-100 pg/mL) of the whole doseresponse curve data was used to estimate the induction effect of IL-6 on CYP1A2 in healthy subjects and in RA patients. This concentration range covered the average baseline IL-6 concentration ranges in both healthy subjects (1.24-6.56 pg/ ml) (16,17,(20)(21)(22)(23)(24)(25)(26) and those in RA patients (3.51-119 pg/mL) (8,10,(14)(15)(16)(17)(18)(19)(20). The PBPK simulation results using the estimated E max and EC 50 value of IL-6 on CYP1A2 induction reasonably captured the moderate modulation effect of IL-6 on caffeine PK in RA patients (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Literature data regarding systemic levels of IL-6 were pooled together to determine the population mean with SD for systemic levels of IL-6 in RA patients (8,10,(14)(15)(16)(17)(18)(19)(20) and in healthy subjects (16,17,(20)(21)(22)(23)(24)(25)(26). The mean or individual IL-6 plasma or serum concentration values from different studies were combined, and associated variability was calculated with R (http://www.r-project.org) and Excel (Microsoft, Redmond, WA).…”

Section: Pooled Analysis Of Systemic Il-6 Concentrations In Ra Patienmentioning

confidence: 99%

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Development of a Physiologically Based Pharmacokinetic Model to Predict Disease-Mediated Therapeutic Protein–Drug Interactions: Modulation of Multiple Cytochrome P450 Enzymes by Interleukin-6

Jiang

Zhuang

et al. 2016

AAPS J

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Abstract. Disease-mediated therapeutic protein-drug interactions have recently gained attention from regulatory agencies and pharmaceutical industries in the development of new biological products. In this study, we developed a physiologically based pharmacokinetic (PBPK) model using SimCYP to predict the impact of elevated interleukin-6 (IL-6) levels on cytochrome P450 (CYP) enzymes and the treatment effect of an anti-IL-6 monoclonal antibody, sirukumab, in patients with rheumatoid arthritis (RA). A virtual RA patient population was first constructed by incorporating the impact of systemic IL-6 level on hepatic and intestinal expression of multiple CYP enzymes with information from in vitro studies. Then, a PBPK model for CYP enzyme substrates was developed for healthy adult subjects. After incorporating the virtual RA patient population, the PBPK model was applied to quantitatively predict pharmacokinetics of multiple CYP substrates in RA patients before and after sirukumab treatment from a clinical cocktail drug interaction study. The results suggested that, compared with observed clinical data, changes in systemic exposure to multiple CYP substrates by anti-IL-6 treatment in virtual RA patients have been reasonably captured by the PBPK model, as manifested by modulations in area under plasma concentration versus time curves for midazolam, omeprazole, S-warfarin, and caffeine. This PBPK model reasonably captured the modulation effect of IL-6 and sirukumab on activity of CYP3A, CYP2C9, CYP2C19, and CYP1A2 and holds the potential to be utilized to assess the modulation effect of sirukumab on the metabolism and pharmacokinetics of concomitant small-molecule drugs in RA patients.

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Section: Discussionmentioning

confidence: 99%

Section: Pooled Analysis Of Systemic Il-6 Concentrations In Ra Patienmentioning

confidence: 99%

Development of a Physiologically Based Pharmacokinetic Model to Predict Disease-Mediated Therapeutic Protein–Drug Interactions: Modulation of Multiple Cytochrome P450 Enzymes by Interleukin-6

Jiang

Zhuang

et al. 2016

AAPS J

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“…Moreover, bacterial respiratory infections, as well as chronic obstructive lung disease, reduce the ability of the organism to clear xenobiotics (Sonne et al, 1985). Other causes of inflammation, such as elective surgery, reduce the activity of CYP3A4 (Haas et al, 2003). Using animal models, it has been shown that various models of inflammation, such as the injection of lipopolysaccharide (LPS), turpentine, and carrageenan depress the activity of the P450 (Cheng and Morgan, 2001;Renton, 2001).…”

mentioning

confidence: 99%

Modulation of Cyp1a2 and Cyp3a6 Catalytic Activities by Serum From Rabbits With a Turpentine-Induced Inflammatory Reaction and Interleukin 6

Kourylko

Fradette²,

Arcand³

et al. 2005

Drug Metab Dispos

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ABSTRACT:Inflammatory reactions reduce the activity of cytochrome P450 isoforms. The aim of the study was to determine the mechanisms underlying the decrease in CYP1A2 and CYP3A6 catalytic activities produced by serum from rabbits with a turpentine-induced inflammatory reaction (S TIIR ) and interleukin 6 (IL-6). S TIIR and IL-6 were incubated with cultured primary hepatocytes from control rabbits (H CONT ), and from rabbits with a turpentine-induced inflammatory reaction (H TIIR ) in the absence or presence of pyrrolidine dithiocarbamate (PDTC), an antioxidant and inhibitor of nuclear factor B transcription; 2-amino-3-methoxyflavone (PD98059), an inhibitor of extracellular signal-related kinase (Erk1/2); 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), an inhibitor of p38MAPK; N -nitro-L-arginine methyl ester, an inhibitor of nitric-oxide synthase 2 (NOS2); the combination of PDTC, PD98059, and SB203580; and genistein, an inhibitor of Janus-associated protein tyrosine kinase (JAK). After 4 and 24 h of incubation of H CONT with S TIIR and IL-6, CYP1A2 activity was reduced without changes in expression; the reduction in activity was partially prevented by the inhibition of JAK, Erk1/2, and NOS2. In H CONT , S TIIR and IL-6 did not affect CYP3A6 activity; however, PDTC reduced CYP3A6 activity by 40 and 80% after 4 and 24 h of incubation. In H TIIR , S TIIR and IL-6 reduced both CYP1A2 and CYP3A6 activities; this decrease is partially prevented by inhibitors of protein tyrosine kinases, Erk1/2, and NOS2. In H TIIR , SB203580 increased CYP3A6 activity in a dose-dependent manner without changes in protein expression. These results show that the signal transduction pathways mediating the decrease in CYP1A2 and 3A6 activity, produced by S TIIR and IL-6, involve JAK, Erk1/2, and NOS2.There is considerable evidence that in humans an inflammatory reaction can diminish the activity of the cytochrome P450 (P450) superfamily . The first documented observation reported that an upper respiratory viral infection in asthmatic children increased theophylline plasma concentrations and half-life (Chang et al., 1978). Actually, numerous reports have documented that influenza infections reduce the rate of biotransformation of theophylline and other drugs (Cheng and Morgan, 2001;Renton, 2001). Moreover, bacterial respiratory infections, as well as chronic obstructive lung disease, reduce the ability of the organism to clear xenobiotics (Sonne et al., 1985). Other causes of inflammation, such as elective surgery, reduce the activity of CYP3A4 (Haas et al., 2003). Using animal models, it has been shown that various models of inflammation, such as the injection of lipopolysaccharide (LPS), turpentine, and carrageenan depress the activity of the P450 (Cheng and Morgan, 2001;Renton, 2001).Already in 1978, the decrease in theophylline clearance was attributed to the down-regulation of P450 isoforms (Renton, 1978). Since then, many reports have confirmed that an inflammatory reaction triggers the release of...

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“…So ist beispielsweise bekannt, dass der H 2 -Antagonist Cimetidin oder der bei HIV-Infektion eingesetzte Proteinasehemmer Ritonavir Inhibitoren der CYP3A4 sind und daher die Eliminationszeit der Substanzen Fentanyl, Sufentanil und Alfentanil verlängert sein kann.Auch Erythromycin und Propofol können die pharmakokinetischen Eigenschaften von Alfentanil durch Interaktion mit der CYP-450-abhängigen Elimination beeinflussen [25,44]. Zudem kann es im Zusammenhang mit chirurgischen Interventionen und der damit verbundenen Inflammation zu einer Abnahme der Aktivität des CYP 3A4 kommen [21].…”

Section: Metabolisierung Der Opioideunclassified

Opioide in der An�sthesie bei Leber- und Niereninsuffizienz

2004

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The pharmacokinetics of opioids are impaired in patients with liver and renal failure. Fentanyl, sufentanil, and alfentanil are metabolized in the liver. The extrahepatic metabolism by renal enzymes is gaining more importance in patients with severe liver disease. Pharmacokinetic effects of single doses of fentanyl and sufentanil are not affected in liver and renal failure; however, continuous infusion of fentanyl may result in accumulation and prolonged opioid effects. Plasma clearance and elimination of alfentanil are reduced in patients with liver failure and its clinical use can therefore not be recommended. A reduction in alfentanil dosing is not necessary in patients with renal failure. Remifentanil is the opioid of choice in patients with liver and renal failure. The clearance of morphine is reduced in liver failure. In renal failure an accumulation of morphine metabolites has been demonstrated, and thus, application of morphine is not recommended in patients with liver and renal failure. A reduction in piritramide dosing is necessary in patients with liver failure.

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Cytochrome P450 3A4 activity after surgical stress

Abstract: Acute inflammation after elective surgery was associated with a significant decline in cytochrome P450 3A4 activity, which is predictive of clinically important changes in the metabolism of commonly used drugs that are substrates for this enzyme.

Cited by 81 publications

References 55 publications

Development of a Physiologically Based Pharmacokinetic Model to Predict Disease-Mediated Therapeutic Protein–Drug Interactions: Modulation of Multiple Cytochrome P450 Enzymes by Interleukin-6

Development of a Physiologically Based Pharmacokinetic Model to Predict Disease-Mediated Therapeutic Protein–Drug Interactions: Modulation of Multiple Cytochrome P450 Enzymes by Interleukin-6

Modulation of Cyp1a2 and Cyp3a6 Catalytic Activities by Serum From Rabbits With a Turpentine-Induced Inflammatory Reaction and Interleukin 6

Opioide in der An�sthesie bei Leber- und Niereninsuffizienz

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