Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Feb 2009
Investigation of PK-PD drug-drug interaction between acenocoumarol and amoxicillin plus clavulanic acid.
A pharmacokinetic-pharmacodynamic (PK-PD) drug-drug interaction between acenocoumarol and amoxicillin + clavulanic acid antibiotic was assessed in eight healthy volunteers, using a population PK-PD) model. Each subject received at day 1 a single dose of 8 mg of acenocoumarol. Then 1 g of amoxicillin + 250 mg of clavulanic acid was given from days 3 to 9. ⋯ An indirect response model was successfully applied to the PK-PD data of acenocoumarol. No covariate, including antibiotic treatment effect, significantly affected PT. Drug-drug interaction was demonstrated at the PK level, without any PD corollary.
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Fundam Clin Pharmacol · Feb 2009
Comparative StudyEffects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice.
The purpose of the present study was to evaluate the nature of the antinociceptive interaction among dexketoprofen (DEX), a mixed inhibitor of the cyclo-oxygenases, and tramadol (TRAM), a weak opioid with monoaminergic activity that inhibits norepinephrine and serotonin re-uptake. We assessed antinociception in the acetic acid writhing test, the tail flick and the formalin (FT) tests, and gastrointestinal transit (GIT) after the administration of a charcoal meal. The analysis of the interaction was carried out using isobolograms and interaction indexes or the fixed-dose method GIT. ⋯ On the inhibition of GIT, a dose-related inhibition was established for TRAM, but not for DEX. Using a fixed-dose protocol, we could demonstrate antagonism between DEX and TRAM on the inhibition of GIT. The results of the present study suggest that a combination of DEX and TRAM in a 1 : 1 proportion could be adequate to use in future clinical trials in humans.