Pharmacokinetics of 300 mg/d Intraperitoneal Daptomycin: New Insight from the DaptoDP Study.

The DaptoDP (NCT 2012-005699-33) study aimed to evaluate the pharmacokinetic parameters of daptomycin (DAP) in peritoneal dialysis-related peritonitis (PDRP) patients following intraperitoneal (IP) administration. The authors have already reported the findings on the 200-mg dosing and present here the follow-up results of the 300-mg dosing. The primary endpoint was a dialysate concentration of DAP above the effective concentration in situ during 6 hours of dwell time i.e., 16 mg/L. Secondary endpoints were to avoid the toxic threshold of 120 mg/L DAP and to be above 16 mg/L DAP for 2 hours in plasma. Pharmacokinetic parameters were evaluated on days 1 and 5. Safety data were evaluated on days 1 to 14 based on clinical and biological parameters. Daptomycin was administered in Nutrineal during 6 hours of dwell time for 14 days plus the usual antibiotic therapy in a separate dwell. Because the 200-mg dosing objectives were not reached, a higher DAP dose of 300 mg was tested in the next 3 patients. Effective dialysate and plasma concentrations were achieved at the 300-mg DAP dose with the plasma concentration well below the toxic threshold, even at steady state, during which the accumulation factor never exceeded 3. The optimal DAP dose of 300 mg daily by the IP route, as determined by the pharmacokinetic data, needs to be clinically confirmed prior to routine use. The peritoneal bioavailability of DAP supports using the IP route as an alternative to the intravenous route for peritonitis and systemic infections.

[Not Available]. / Arrêt soudain des médicaments spécifiques de la démence au stade modéré à sévère de la maladie d'Alzheimer en institution : étude pilote longitudinale descriptive.

PURPOSE: The modalities for anti-dementia drugs' discontinuation are not consensual. OBJECTIVE: The objectives of the study were the followings, describe: i) the reasons for discontinuation of anti-dementia drugs of patients treated in a residency for dependent elderly people, ii) security of sudden discontinuation, iii) evolution of troubles. METHODS: Our longitudinal descriptive pilot study aimed at observing consequences of the sudden discontinuation of anti-dementia drugs in a population with a moderate to severe stage of Alzheimer's disease. The study took place in a French residency for dependent elderly people, treated with at least one of the following treatments: rivastigmine, donepezil, galantamine and/or memantine. Based on multidisciplinary decision, as recommended, patient's anti-dementia treatment have been stopped or not. Criteria have been collected for 6months and compared between the two groups: safety, motivation for discontinuation, score mini-mental state examination (MMSE), psycho-behavior criteria and finally the concomitant prescription of psychotropic drugs. RESULTS: Thirty-three patients were included: the revaluation of anti-dementia treatment led to 22 discontinuations and 11 continuations. Motivations to stop antidementia treatment were: too advanced dementia (48%), lack of therapeutic benefit (28%) or too much of psychotropic medications (24%). The sudden discontinuation was well tolerated with no withdrawal syndrome observed. The variation of MMSE at 6months was -1.8 (SD 2.2) in the discontinuation group (n=14) versus -2.2 (SD 2.0) in the continuation group (n=6). The psycho-behavior disorders have not been aggravated. A reduction in number of psychotropic drugs in the discontinuation group was observed. CONCLUSION: In this pilot study, the revaluation in accordance with the recommendations of the Haute autorité de santé (HAS) led to the discontinuation of two third of anti-dementia drugs. Safety of sudden discontinuation of MSD remains to be studied.