Objectives Although levetiracetam presents an easy dosing and tolerability, therapeutic drug monitoring may be recommended in certain situations. Measurement of levetiracetam in serum plasma is commonly done by high performance liquid chromatography (HPLC). After ARK Diagnostics marketed an enzyme immunoassay (IA) for levetiracetam in serum or plasma, automated determinations are possible. In this study, the performance of this immunoassay and the impact of automation on the follow-up in patients treated with levetiracetam is evaluated. We also detected those subpopulations of patients who may benefit the most from this therapeutic drug monitoring. Methods Samples from 50 outpatients diagnosed with epilepsy and treated with levetiracetam were collected. This new IA was performed on the Architect c4000 analyser and compared with the HPLC. Then, a retrospective observational study that included serum samples of levetiracetam for 24 months, was conducted to evaluate the impact of automattion and the influence of some variables (age, sex, renal function, and coadministration of valproic acid and glucuronidationinducing drugs) in levetiracetam apparent oral clearance (CLp/F) by a multivariate linear regression. results The mean high-performance liquid chromatography quantified concentration (CpHPLC) was 18.43 mcg/mL (95% CI: 15.48 to 21.39) and immunoassay concentration (CpEI) was 18.35 mcg/mL (95% CI: 15.20 to 21.50) (P=0.861). The Pearson's linear correlation coefficient obtained in the analysis was r 2 =0.88, according to the following equation: CpHPLC=−0.29+1.01 CpEI. The intraclass correlation coefficient was 0.95 (95% CI: 0.91 to 0.97). After IA implementation, the number of levetiracetam determinations increased in 76.27%. The median of Clp/F was higher (P<0.001) in inducers (4.36 L/h; IQR:3.29-5.44) and lower (P<0.001) in glomerular filtration rate (GFR) <60 mL/min (2.7 L/h; IQR: 0.58-3.85). Conclusions The Ark method performed on the Architect is fully acceptable and can be used routinely to measure levetiracetam plasmatic concentration levels. It has demonstrated the need for closer monitoring in patients with renal failure or co-administration of glucuronidation-inducing drugs.

Data of sex, age, diagnostic, previous biological treatment, start date and last dispensation date were collected.Il-17's persistence was calculated in months using the Kaplan-Meier method and log-rank test to compare the survival along diagnostic, drug and line of treatment using SPSS Statistics, considering a p value <0.05. Results A total of 80 patients were included (33 with ixekizumab (60% Ps, 40% PsA) and 47 with secukinumab (49% Ps, 51% PsA). 36% were men, median age 54 (IQR 42-60) years. 31.25% were treated as first line, 13.75% as second line and 55% at third line or more with a median of two previous biological drugs.46.25% discontinued treatment during the study (60% ixekizumab, 50% secukinumab). 55% of patients had been treated for more than a year with IL-17 (35% of them for more than 2 years) and the rest 45% interrupted treatment before completing a year (58% for less than 6 months).IL-17's persistence was 24.1 months (95% CI 17.9 to 30.2) vs 30.9 months (95% CI 24.3 to 37.4) for ixekizumab and secukinumab, respectively, and did not show a significant difference (p=0.774).Comparing between groups, there were no differences in ixekizumab's persistence in Ps vs PsA (24.5 vs 14.2 months, p=0.97), secukinumab's persistence in Ps vs PsA (32.5 vs 24.3 months, p=0.6), Ps' persistence of ixekizumab vs secukinumab (p= 0.79) and PsA's persistence of ixekizumab vs secukinumab (p=0.83). Regarding the persistence of the treatment line this was similar in each group, and did not show any statistical differences. Conclusion and relevanceBoth IL-17 inhibitors show a similar and considerable persistence of nearby 30 months globally. No significant differences were found either between between the drugs, diagnostics nor line of treatment.

ObjectivesTo compare vancomycin dosage adjustment by evaluating trough concentrations (Ctrough) of vancomycin and its pharmacokinetic/pharmacodynamic (PK/PD) correlation (AUC/MIC ≥400).MethodsA retrospective study of 52 adult haematological patients and 29 ICU patients was carried out. Dosage adjustment was performed in routine clinical practice with Ctrough​​ and then compared using a PK/PD model. The probability of achieving the PK/PD target associated with the success of antimicrobial therapy was evaluated. When the susceptibility of the organism responsible for infection is not known, Monte Carlo simulation calculates the cumulative fraction of response (CFR) from the distribution of MIC values. Values of CFR >90% represent an optimal achieved regimen against a population of microorganisms.ResultsAccording to dosage adjustment performed ​​with Ctrough, in haematological patients the dose of vancomycin was increased in 65.4% compared with an increase in 53.8% of patients with the PK/PD model. No dose adjustment was needed in 21.1% of patients using Ctrough compared with 7.7% with the PK/PD model and in 13.5% of patients using Ctrough determination and in 38.5% of patients with the PK/PD model the dose was reduced. For ICU patients the dosage adjustment made ​​with Ctrough resulted in an increased dose of vancomycin in 79.4% of patients compared with 41.4% with the PK/PD model. No dose adjustment was needed in 3.4% of patients using Ctrough in comparison with 13.8% with the PK/PD model, and the dose was reduced in 17.2% of patients using Ctrough determination and in 44.8% with the PK/PD model.ConclusionsData for bacterial susceptibility combined with measured data for antibiotic concentrations using a PK/PD model predict and improve the dosage adjustment for individual patients. A larger study with more complete datasets are needed for validation before it can be fully introduced into clinical practice.

BackgroundThe pharmacokinetic/pharmacodynamic (PK/PD) index for the efficacy of linezolid is defined as the area under the plasma drug concentration-time curve (AUC24)/minimum inhibitory concentration (MIC).PurposeTo establish linezolid dosing regimen to achieve the expected PK/PD target using THE Monte Carlo simulation for successful therapy.Material and methodsThe pharmacokinetic parameters of linezolid were obtained from published studies. MIC data were collected of our centre for the years 2013 and 2014 for Staphylococcus aureus and coagulase negative staphylococcus (CNS) isolates. The pharmacokinetic parameters were defined as a log normal distribution in the Monte Carlo simulation, and in the case of MIC, a discrete distribution. A Monte Carlo simulation with 10 000 subjects was performed using the SimulAr program. Acumulative fraction of response (CFR) was calculated (CFR values of >90% represent an optimal regimen). Optimal AUC/MIC ≥100 was considered.ResultsAfter literature review, a population pharmacokinetic study of linezolid was selected in adult patients suffering from Gram positive bacterial infections. A one compartment PK model was used with a first order elimination process and the final equation model for Linezolid clearance (ClLin)=0.0258xCreatinine clearance (ClCr) (L/h)+2.03 with interindividual variability of 30.5%. ClCr was estimed using the Cockcroft and Gault method. MICs for S aureus were fixed at 0.5, 1, 2, 4 and 8 μl/mL, with a relative distribution of 0.0075, 0.3387, 0.4807, 0.1667 and 0.0064, respectively. For CNS, MICs were fixed at 0.5, 1, 2 and 4 μl/mL with a relative distribution of 0.3267, 0.6707, 0.0013 and 0.0013, respectively. The simulation analysis for S aureus suggested doses of 900, 1200, 1800 and 2400 mg/day for ClCr <25, 25–60, 60–125 and >125 mL/min, respectively. For CNS, doses of 600, 900 and 1200 mg/day were suggested for ClCr <60, 60–125 and >125 mL/min, respectively.ConclusionAccording to the population pharmacokinetic model and the MIC chosen, linezolid doses should be individualised based on patient ClCr and strain of staphylococcus spp isolated.References and/or AcknowledgementsMatsumoto, Shigemi A, Takeshita A, et al. Int J Antimicrob Agents 2014;44:242-7No conflict of interest.

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