Biomedical subjects

Alain Dauphin

Publications and source records attributed to Alain Dauphin.

3 recordsLinked to original sources

PubMed2006

A kinetic-pharmacodynamic model for clinical trial simulation of antidepressant action: application to clomipramine-lithium interaction.

A generic kinetic-pharmacodynamic (K-PD) model to describe the response to treatment assessed by a clinical score for depressed patients treated by antidepressants alone or combined with a drug that shortens the lag-time before effect was developed. The aims of this study were: (1) to verify model's ability to characterize clinical data, (2) to evaluate several statistics to summarize the clinical effect, (3) to compare the analysis based on these statistics to the conventional intent-to-treat analysis and (4) to determine the optimal dates of clinical assessment. The population K-PD model was fitted to the individual data from a randomized clinical trial assessing the efficacies of clomipramine and placebo or clomipramine and lithium to treat major depression in 141 patients. The K-PD model was able to fit the individual data even in the case of oscillating score profiles. The interindividual coefficient of variation of the model parameters ranged from 33 to 161%. The statistical analysis based on the secondary parameters yielded conclusions comparable to those of the conventional intent-to-treat analysis. The population model was then used for a clinical trial simulation. According to the simulation, the most sensitive summary statistics for detecting a difference between lithium and placebo were the fractional reduction of depression and the proportion of responders. The optimal dates to assess these parameters were day 9 and 11 respectively. The K-PD model might serve as a tool for clinical trial planning in the field of research on antidepressants and their facilitators.

Antidepressive Agents↗

PubMed2005

A mathematical model for paroxetine antidepressant effect time course and its interaction with pindolol.

Although selective 5-HT reuptake inhibitors (SSRIs) block monoamine uptake within hours of administration to patients, their full clinical effect does not appear until 2-4 weeks after treatment onset. Pindolol, a betablocker with weak partial 5-HT1A receptor agonist activity has been shown to produce a more rapid onset of antidepressant action of SSRIs. However, the optimal dosing schedule of pindolol remains controversial. Building on a set-point model described previously for the hypothermic effect of 5-HT agonists, we have developed a model based on the concept of homeostatic control mechanisms, in which SSRIs exert their antidepressant effect by increasing the transduction set-point of the postsynaptic 5-HT1A receptor, and pindolol exerts its effect by increasing the rate of feedback mechanisms. The predictive distribution of the proportion of responders at each day of measurement (based on population simulation from the model) was not significantly different from the proportions observed in two published clinical trials, one with fluoxetine, the other with paroxetine alone or combined with pindolol. The model was applied to the simulation of paroxetine response (clinical score) time course with or without pindolol, after administration of different doses of each drug. The simulated total scores on the MADR scale obtained after treatment with paroxetine alone (20 mg/day) or paroxetine (20 mg/day) with different doses of pindolol (1.5, 7.5 and 37.5 mg/day) support that the reason for inconstant pindolol efficacy is that the 7.5 mg dose is too low. The model might be useful as a basis for clinical trial simulation.

Algorithms↗

PubMed2003

[Infusion solutions].

Infusion solutions or preparations for intravenous administration have been developed since 1830 after the work of Thomas Latta. This particular pharmaceutical form, which brings large accounts of liquid (100 to 3000 ml) and nourishes, equilibrates, hydrates, clears, serves as a vehicule for many drugs and allows organ storage, has had a considerable development owing to its successes in a number of severe diseases and because it has supported the emergence of critical care and intensive care medicine. This form has an unappreciated story. It was first used in hospitals but it is now manufactured by the pharmaceutical industry after a long series of technical improvements and galenic innovations bringing solutions to the problems successively encountered (microbial contamination, embolism, blood alteration, "saline fever", degradation and adsorption of drugs, allergic shock...) and answers to the new requirements resulting from progresses in physiology and biology (hydroeletrolytic support, plasma expansion, energy supply, acidobasic homeostasis, malnutrition...). This story is depicted with respect to the indications, the formulation, the infusion devices from the origin to nowadays.

History, 19th Century↗