Source:http://linkedlifedata.com/resource/pubmed/id/10217331
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
1999-6-29
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| pubmed:abstractText |
The time course and concentration-effect relationship of parasympatholytic effects of three anticholinergic drugs were investigated using spectral analysis of heart rate (HR) variability. Single intravenous (i.v.) doses of atropine (10 microg/kg), glycopyrrolate (5 microg/kg), scopolamine (5 microg/kg), and placebo were given to eight healthy volunteers in a double-blind, randomized cross-over study. Electrocardiogram (ECG) was recorded at baseline and 2.5, 5, 10, 20, and 30 minutes, and 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration, while the subjects breathed at a fixed 0.25 Hz frequency. The powers of two frequency bands (low frequency [LF] = 0.07-0.15 Hz and high frequency [HF] = 0.15-0.40 Hz) were calculated using stationary time series of R-R intervals (RRI) free from ectopic beats. To perform pharmacokinetic-pharmacodynamic (PK-PD) modeling, venous plasma drug concentrations were measured. Atropine and glycopyrrolate, and, to a lesser extent, scopolamine induced decreases in HF power and increases in LF/HF ratio of HR variability, indicating parasympatholytic activity and corresponding changes in sympathovagal balance. Maximal average decreases in HF power were 99%, 94%, and 82%, respectively, but in two scopolamine subjects, a parasympathomimetic effect was dominant. Interindividual variability was least for the Hayano index of HF power (square root (RRI HF-power)/RRI*100), and profound and consistent decreases were seen after atropine and glycopyrrolate. Pharmacokinetics were best fitted to a two-compartment open model, and effect compartment link modeling using the Hayano index was performed with the atropine and glycopyrrolate data. The best description of the PK-PD relationship for both drugs was achieved using the sigmoidal Emax model. Mean (+/-SD) EC50, sigmoidicity factor (gamma), and equilibration rate constant (k(e0)) estimates were 1.35 (+/-0.27) ng/mL, 6.07 (+/-1.98) and 11.0 (+/-5.28) l/h for atropine and 1.35 (+/-0.49) ng/mL, 4.34 (+/-1.55) and 2.26 (+/-0.81) l/h for glycopyrrolate. Spectral analysis of HR variability appears to be a powerful tool in monitoring parasympatholytic drug activity. A sigmoidal Emax model with an extremely steep concentration-response relationship was revealed for atropine and glycopyrrolate. The effects of scopolamine were more incongruous.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Atropine,
http://linkedlifedata.com/resource/pubmed/chemical/Cholinergic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Glycopyrrolate,
http://linkedlifedata.com/resource/pubmed/chemical/Parasympatholytics,
http://linkedlifedata.com/resource/pubmed/chemical/Scopolamine Hydrobromide
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
|
| pubmed:issn |
0163-4356
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
21
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
141-51
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10217331-Adult,
pubmed-meshheading:10217331-Atropine,
pubmed-meshheading:10217331-Blood Pressure,
pubmed-meshheading:10217331-Cholinergic Antagonists,
pubmed-meshheading:10217331-Cross-Over Studies,
pubmed-meshheading:10217331-Dose-Response Relationship, Drug,
pubmed-meshheading:10217331-Double-Blind Method,
pubmed-meshheading:10217331-Electrocardiography,
pubmed-meshheading:10217331-Glycopyrrolate,
pubmed-meshheading:10217331-Heart Rate,
pubmed-meshheading:10217331-Humans,
pubmed-meshheading:10217331-Injections, Intravenous,
pubmed-meshheading:10217331-Male,
pubmed-meshheading:10217331-Models, Biological,
pubmed-meshheading:10217331-Parasympathetic Nervous System,
pubmed-meshheading:10217331-Parasympatholytics,
pubmed-meshheading:10217331-Reference Values,
pubmed-meshheading:10217331-Respiration,
pubmed-meshheading:10217331-Scopolamine Hydrobromide,
pubmed-meshheading:10217331-Time Factors
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| pubmed:year |
1999
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| pubmed:articleTitle |
Spectral analysis of heart rate variability as a quantitative measure of parasympatholytic effect--integrated pharmacokinetics and pharmacodynamics of three anticholinergic drugs.
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| pubmed:affiliation |
Department of Clinical Pharmacology, Turku University Hospital, Finland.
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| pubmed:publicationType |
Journal Article,
Clinical Trial,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't
|