Abstract:
:Erythromycin inhibits the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL6) induced by heat-killed Streptococcus pneumoniae in human whole blood ex-vivo. The objective of the present study was to determine and characterize the concentration-effect relationship of this phenomenon in order to predict its possible clinical relevance. Six healthy volunteers received a single intravenous dose of 1000 mg erythromycin. Blood samples were obtained up to 4 h after drug administration. Samples were assayed for erythromycin concentrations and (after heat-killed Streptococcus pneumoniae stimulation) for TNF-alpha and IL6 concentrations. Effect vs. time data from individual subjects were fitted to the indirect response model with an Emax concentration-effect relationship. Simulations of these effects were performed for therapeutic intravenous and oral erythromycin dosage regimens. The geometric means of the values of Kin, Kout and EC50 were 15.4 microg/h, 0.82/h, 9.4 mg/L for TNF-alpha and 321 microg/h, 2.02/h, 18.3 mg/L for IL6. Simulations revealed a maximal inhibition of TNF-alpha concentrations of 35%, 50%, 16% and 27% at erythromycin dosages of 500 mg i.v., 1000 mg i.v., 500 mg p.o and 1000 mg p.o. q 6 h, respectively, whereas a maximal inhibition of IL6 of 29%, 44%, 13% and 22% are predicted for the respective regimens. The inhibitory effect of erythromycin on TNF-alpha and IL6 production can be adequately described by the indirect response model with an Emax concentration-effect relationship. Simulations predicted a substantial decrease of production of these cytokines at intravenous and to a much lesser extent at oral erythromycin dosage regimens.
journal_name
Fundam Clin Pharmacoljournal_title
Fundamental & clinical pharmacologyauthors
Guchelaar HJ,Schultz MJ,van der Poll T,Koopmans RPdoi
10.1046/j.1472-8206.2001.00054.xsubject
Has Abstractpub_date
2001-12-01 00:00:00pages
419-24issue
6eissn
0767-3981issn
1472-8206pii
054journal_volume
15pub_type
杂志文章abstract::Adverse reactions to antipsychotic drugs (APs) have been attributed to oxidative stress. Sulforaphane (SF) is a potent antioxidant that protects against dopaminergic cell death. We examined the protective properties of SF against AP-induced oxidative stress in dopaminergic neuroblastoma cells. Human neuroblastoma SK-N...
journal_title:Fundamental & clinical pharmacology
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abstract::The H1-histaminergic agonists 2-pyridylethylamine (2-PEA) and 2-methylhistamine relaxed potassium-constricted, perfused, rabbit middle cerebral arteries at low concentrations (3 x 10(-11) to 3 x 10(-8) M) and constricted them at high concentrations (3 x 10(-7) to 3 x 10(-4) M). The relaxation and the contraction were ...
journal_title:Fundamental & clinical pharmacology
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