Document Detail

Pharmacokinetic-pharmacodynamic modeling of the effects of clonidine on pain threshold, blood pressure, and salivary flow.
MedLine Citation:
PMID:  1623908     Owner:  NLM     Status:  MEDLINE    
Although clonidine analgesia appears to be mediated by the same central alpha 2-adrenoceptors that mediate its hypotensive effect, it is short-lasting when compared to the fall in blood pressure. This has been investigated by combined pharmacokinetic-pharmacodynamic analysis in 10 healthy volunteers who received (double-blind and crossover) clonidine 200 micrograms orally + placebo i.v. and clonidine orally + naloxone i.v. (2.8 mg/5 h). Analgesia was assessed by measuring the subjective (VAS) and objective (RIII) pain thresholds after transcutaneous electrical stimulations of the sural nerve; the mean arterial blood pressure (MAP), salivary flow (SF), and plasma clonidine concentrations were also monitored. A combined pharmacokinetic (first order absorption - 1 compartment) - pharmacodynamic (linear) model, including a hypothetical effect compartment with and without tolerance, were fitted to the data. Clonidine and clonidine + naloxone increased subjective and objective pain thresholds for 4 h. The concentration-effect plot for MAP showed distinct hysteresis. The t1/2s for effect compartment equilibration were 29 and 42 min for clonidine + naloxone and clonidine. The concentration-effect curves for RIII had the same shape as MAP but the starting hysteresis suddenly collapsed, suggesting acute tolerance. The best fit was obtained with a model where the linear relationship between concentration in the effect compartment and analgesia changed acutely after the third hour. The short-lived analgesia was probably related to an acute change in pain sensitivity induced by food, suggesting that it is not mediated solely by the alpha 2-adrenoceptors responsible for hypotension.
H C Porchet; P Piletta; P Dayer
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article    
Journal Detail:
Title:  European journal of clinical pharmacology     Volume:  42     ISSN:  0031-6970     ISO Abbreviation:  Eur. J. Clin. Pharmacol.     Publication Date:  1992  
Date Detail:
Created Date:  1992-08-10     Completed Date:  1992-08-10     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  1256165     Medline TA:  Eur J Clin Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  655-61     Citation Subset:  IM    
Division of Clinical Pharmacology, University Hospital, Geneva, Switzerland.
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MeSH Terms
Analgesics / pharmacokinetics*,  pharmacology*
Blood Pressure / drug effects
Clonidine / pharmacokinetics*,  pharmacology*
Double-Blind Method
Models, Biological
Salivation / drug effects
Reg. No./Substance:
0/Analgesics; 4205-90-7/Clonidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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