4 research outputs found
Novel population pharmacokinetic model for Linezolid in critically Ill patients and evaluation of the adequacy of the current dosing recommendation
Antimicrobial treatment in critically ill patients remains challenging. The aim of this study
was to develop a population pharmacokinetic model for linezolid in critically ill patients and to
evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were
included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and
effluent samples were drawn after linezolid administration at defined time points, and linezolid
levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3.
The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets
was calculated (AUC24/MIC > 80 and 100% T>MIC). A two-compartment model best described the
pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the
extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose
of linezolid did not cover infections caused by pathogens with MIC â„ 2 mg/L. Continuous infusion
may be an alternative, especially when renal function is preserved
Seafood Consumption, Omega-3 Fatty Acids Intake, and Life-Time Prevalence of Depression in the PREDIMED-Plus Trial
Background: The aim of this analysis was to ascertain the type of relationship between fish
and seafood consumption, omega-3 polyunsaturated fatty acids (Ï-3 PUFA) intake, and depression
prevalence. Methods: Cross-sectional analyses of the PREDIMED-Plus trial. Fish and seafood
consumption and Ï-3 PUFA intake were assessed through a validated food-frequency questionnaire.
Self-reported life-time medical diagnosis of depression or use of antidepressants was considered
as outcome. Depressive symptoms were collected by the Beck Depression Inventory-II. Logistic
regression models were used to estimate the association between seafood products and Ï-3 PUFA
consumption and depression. Multiple linear regression models were fitted to assess the association
between fish and long-chain (LC) Ï-3 PUFA intake and depressive symptoms. Results: Out of
6587 participants, there were 1367 cases of depression. Total seafood consumption was not associated
with depression. The odds ratios (ORs) (95% confidence intervals (CIs)) for the 2nd, 3rd, and 4th
quintiles of consumption of fatty fish were 0.77 (0.63â0.94), 0.71 (0.58â0.87), and 0.78 (0.64â0.96),
respectively, and p for trend = 0.759. Moderate intake of total LC Ï-3 PUFA (approximately
0.5â1 g/day) was significantly associated with a lower prevalence of depression. Conclusion: In our
study, moderate fish and LC Ï-3 PUFA intake, but not high intake, was associated with lower odds
of depression suggesting a U-shaped relationship
Novel population pharmacokinetic model for Linezolid in critically Ill patients and evaluation of the adequacy of the current dosing recommendation
Antimicrobial treatment in critically ill patients remains challenging. The aim of this study
was to develop a population pharmacokinetic model for linezolid in critically ill patients and to
evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were
included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and
effluent samples were drawn after linezolid administration at defined time points, and linezolid
levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3.
The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets
was calculated (AUC24/MIC > 80 and 100% T>MIC). A two-compartment model best described the
pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the
extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose
of linezolid did not cover infections caused by pathogens with MIC â„ 2 mg/L. Continuous infusion
may be an alternative, especially when renal function is preserved
Population Pharmacokinetics of Meropenem in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy
BACKGROUND AND OBJECTIVE:
Meropenem is a carbapenem antibacterial frequently prescribed for the treatment of severe infections in critically ill patients, including those receiving continuous renal replacement therapy (CRRT). The objective of this study was to develop a population pharmacokinetic model of meropenem in critically ill patients undergoing CRRT.
PATIENTS AND METHODS:
A prospective, open-label study was conducted in 20 patients undergoing CRRT. Blood and dialysate-ultrafiltrate samples were obtained after administration of 500 mg, 1000 mg or 2000 mg of meropenem every 6 or 8 hours by intravenous infusion. The data were analysed under the population approach using NONMEM version V software. Age, bodyweight, dialysate plus ultrafiltrate flow, creatinine clearance (CL(CR)), the unbound drug fraction in plasma, the type of membrane, CRRT and the patient type (whether septic or severely polytraumatized) were the covariates studied.
RESULTS:
The pharmacokinetics of meropenem in plasma were best described by a two-compartment model. CL(CR) was found to have a significant correlation with the apparent total clearance (CL) of the drug during the development of the covariate model. However, the influence of CL(CR) on CL differed between septic and polytraumatized patients (CL = 6.63 + 0.064 x CL(CR) for septic patients and CL = 6.63 + 0.72 x CL(CR) for polytraumatized patients). The volume of distribution of the central compartment (V(1)) was also dependent on the patient type, with values of 15.7 L for septic patients and 69.5 L for polytraumatized patients. The population clearance was 15 L/h, and the population apparent volume of distribution of the peripheral compartment was 19.8 L. From the base to the final model, the interindividual variabilities in CL and the V(1) were significantly reduced. When computer simulations were carried out and efficacy indexes were calculated, it was shown that polytraumatized patients and septic patients with conserved renal function may not achieve adequate efficacy indexes to deal with specific infections. Continuous infusion of meropenem is recommended for critically septic patients and polytraumatized patients when pathogens with a minimum inhibitory concentration (MIC) of > or =4 mg/L are isolated. Infections caused by pathogens with an MIC of > or =8 mg/L should not be treated with meropenem in polytraumatized patients without or with moderate renal failure because excessive doses of meropenem would be necessary.
CONCLUSION:
A population pharmacokinetic model of meropenem in intensive care patients undergoing CRRT was developed and validated. CL(CR) and the patient type (whether septic or polytraumatized) were identified as significant covariates. The population pharmacokinetic model developed in the present study has been employed to recommend continuous infusion protocols in patients treated with CRRT