Altered Theophylline Pharmacokinetics During Acute Respiratory Viral Illness

Chang, Ki Churl; Lauer, Brian A.; Bell, Thomas D.; Chai, Hyman

doi:10.1016/s0140-6736(78)90305-7

Cited by 263 publications

(78 citation statements)

References 2 publications

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“…In one study, the plasma half-life of theophylline was determined during and 1 month after serologically confirmed upper-respiratory-tract viral illness in six children with chronic asthma. In this group the plasma theophylline half-life (mean = 419.8 minutes) was significantly longer during the acute stage of illness than 1 month later (mean = 249.9 minutes) (Chang et al, 1978). Serum theophylline levels also increase, often to toxic levels, following influenza vaccination (Renton et al, 1980).…”

Section: Evidence For Potential Phenoconversion Of Dmes In Other Inflmentioning

confidence: 89%

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Shah¹,

2014

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Phenoconversion transiently converts genotypic extensive metabolizers (EMs) into phenotypic poor metabolizers (PMs) of drugs, potentially with corresponding changes in clinical response. This phenomenon, typically resulting from coadministration of medications that inhibit certain drug metabolizing enzymes (DMEs), is especially well documented for enzymes of the cytochrome P450 family. Nonclinical evidence gathered over the last two decades also strongly implicates elevated levels of some proinflammatory cytokines, released during inflammation, in down-regulation of drug metabolism, especially by certain DMEs of the P450 family, thereby potentially causing transient phenoconversion. Clinically, phenoconversion of NAT2, CYP2C19, and CYP2D6 has been documented in inflammatory conditions associated with elevated cytokines, such as human immunodeficiency virus infection, cancer, and liver disease. The potential of other inflammatory conditions to cause phenoconversion has not been studied but experimental and anecdotal clinical evidence supports infectioninduced down-regulation of CYP1A2, CYP3A4, and CYP2C9 as well. Collectively, the evidence supports a hypothesis that certain inflammatory conditions associated with elevated proinflammatory cytokines may cause phenoconversion of certain DMEs. Since inflammatory conditions associated with elevated levels of proinflammatory cytokines are highly prevalent, phenoconversion of genotypic EM patients into transient phenotypic PMs may be more frequent than appreciated. Since drug pharmacokinetics, and therefore the clinical response, is influenced by DME phenotype rather than genotype per se, phenoconversion (whatever its cause) can have a significant impact on the analysis and interpretation of genotype-focused clinical outcome association studies. There is a risk that focusing on genotype alone may miss important associations between clinical outcomes and DME phenotypes, thus compromising future prospects of personalized medicine.

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Section: Evidence For Potential Phenoconversion Of Dmes In Other Inflmentioning

confidence: 89%

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Shah¹,

2014

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“…Changes in P450-mediated drug clearance, associated with inflammation, have been demonstrated in humans with various infections including influenza and HIV (Chang et al, 1978;Jones et al, 2010), as well as in patients with cancer and heart failure (Frye et al, 2002;Rivory et al, 2002). In both humans and laboratory animals, most P450 enzymes studied are down-regulated (Aitken et al, 2006), primarily by pretranslational mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Selective Modulation of Hepatic Cytochrome P450 and Flavin Monooxygenase 3 Expression duringCitrobacter rodentiumInfection in Severe Combined Immune-Deficient Mice

et al. 2012

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“…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).…”

Section: Introductionmentioning

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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Altered Theophylline Pharmacokinetics During Acute Respiratory Viral Illness

Cited by 263 publications

References 2 publications

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Selective Modulation of Hepatic Cytochrome P450 and Flavin Monooxygenase 3 Expression duringCitrobacter rodentiumInfection in Severe Combined Immune-Deficient Mice

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

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