Pharmacokinetic/Pharmacodynamic Modelling of Roxithromycin for the Inhibitory Effect of Tumour Necrosis Factor-Alpha and Interleukin-6 Production in Dogs
Summary The objective of the present study was to determine and characterize the relationship between the plasma concentration of roxithromycin, and its inhibitory effect on cytokine production, in order to predict its possible clinical relevance. Six healthy beagle dogs received a single intravenou...
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Published in | Journal of veterinary medicine. Series A Vol. 53; no. 8; pp. 394 - 398 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.10.2006
Hindawi Limited |
Subjects | |
Online Access | Get full text |
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Summary: | Summary
The objective of the present study was to determine and characterize the relationship between the plasma concentration of roxithromycin, and its inhibitory effect on cytokine production, in order to predict its possible clinical relevance. Six healthy beagle dogs received a single intravenous dose of 20‐mg roxithromycin per kg body weight. Blood samples were obtained at different time points. The plasma was analysed with respect to roxithromycin, tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). The concentration–effect relationship was explored by modelling the data using two compartmental model and an indirect response model with an Emax concentration–effect relationship. The estimated pharmacokinetic parameters (geometric mean) were as follows: Vc = 2.59 l; k10 = 0.08/h; k12 = 0.26/h; k21 = 0.40/h. The pharmacodynamic parameters (geometric mean) for the inhibitory effect on cytokine production induced by heat‐killed Staphylococcus aureus (HKSA) were for TNF‐α (kin = 1.42 μg/h; kout = 1.10 μg/h; EC50 > 5.69 mg/l) and for IL‐6 (kin = 2.31 μg/h; kout = 2.04 μg/h; EC50 = 21.07 mg/l) production, respectively. The inhibitory effect of roxithromycin on production can be adequately described by the indirect response model with an Emax concentration–effect relationship. |
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Bibliography: | ark:/67375/WNG-C0218P0W-M istex:510CB9BE36D8D5B6B4A0ABEEF7A72D9712855D44 ArticleID:TBED852 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0931-184X 1865-1674 1439-0442 1865-1682 |
DOI: | 10.1111/j.1439-0442.2006.00852.x |