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 · Dec 2008
Clinical TrialIntegration of modelling and simulation into the development of intravenous busulfan in paediatrics: an industrial experience.
Busulfan (Bu) is commonly used in preparative conditioning regimen prior to bone marrow transplantation in infants (< 1 year old), children and adolescents (up to 17 years old). The clinical development of an intravenous form of busulfan (Busilvex) was based on pharmacokinetic (PK) modeling and simulation techniques. A retrospective population PK analysis was initially performed from a first study in 24 pediatric patients (0.45-16.7 years old) and a log-linear relationship between body weight and Busilvex clearance was demonstrated with no age-dependency. ⋯ The benefit from this new dosing strategy was validated in a second trial including 55 children (0.30-17.2 years old). This prospective trial confirmed the previous simulations: an efficient therapeutic targeting whatever the patient's age or body weight. Over 80% of the children were within the desired plasma exposure window, and the initial PK model was validated on the confirmatory dataset.
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Critically ill patients, not infrequently present alterations of physiological parameters that determine the success/failure of therapeutic interventions as well as the final outcome. Sepsis and polytrauma are two of the most common and complex syndromes occurring in Intensive Care Unit (ICU) and affect drug absorption, disposition, metabolism and elimination. Pharmacological management of ICU patients requires consideration of the unique pharmacokinetics associated with these clinical conditions and the likely occurrence of drug interaction. Rational adjustment in drug choice and dosing contributes to the appropriateness of treatment of those patients.
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The incidence of sepsis, the combination of a systemic inflammatory response syndrome and documented infection, is as high as up to 95 cases per 100,000 people per year. The understanding of the pathophysiology of sepsis has much increased over the last 20 years. However, sepsis combined with shock is still associated with a high mortality rate varying from 35 to 55%. ⋯ The possible beneficial role of strict glucose control is also addressed. Since many drug intervention studies were negative, lessons should be learned from earlier experiences for future trials. Source control and level of intensive care should be eliminated as confounders.
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Fundam Clin Pharmacol · Jun 2008
Abstracts of the 12th Annual Meeting of the French Society of Pharmacology and Therapeutics, the 75th Annual Meeting of the Society of Physiology, the 29th Pharmacovigilance Meeting, the 9th APNET Seminar and the 6th CHU CIC Meeting. April 9-11, 2008, Clermont-Ferrand, France.