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Objective: In this study, we aimed to assess main factors influencing the Valproic Acid (V.Acid) plasma trough levels (C0) and to determine their degree of influence on V.Acid C0 in children with epilepsy who had Therapeutic Drug Monitoring (TDM)., Methods: We conducted an observational study in the Department of Clinical Pharmacology including patients with generalized seizures' epilepsy aged between two and 18 years. Only the children that had benefited from at least two V.Acid C0 determinations were included. First, we assessed daily dose optimization, performed by the practitioners. Then we divided our population into two groups: group A with a final V.Acid C0 in the therapeutic range (TR) and group B with a final V. Acid C0 outside the TR to find out factors influencing V.Acid C0 journey., Results: We included 805 patients (2537 V.Acid C0). The median age was 6.24 years and the sex ratio (M/F) was 1.45. The median V.Acid normalized daily dose was 27.27mg/kg/day and the median V.Acid C0 was 57µg/mL. The children's first V.Acid C0 was in the TR in 59.4% and V.Acid daily dose optimization was performed by the practitioners in 72.3%. Comparing GroupA and B, we found that age and the number of V.Acid C0 determinations increases the chance to reach the TR by respectively 3.79% and 7.39%., Conclusion: Older children who benefit from higher number of performed V.Acid C0 were more likely to reach the TR. In children who beneficiate from a TDM of V.Acid, close follow-up is mandatory to reach and maintain therapeutic V.Acid C0.

Introduction: Digoxin is a cardiac glycoside, used to control rapid ventricular rates in atrial fibrillation and to reduce the hospitalizations due to heart failure. Digoxin has a narrow therapeutic range. So, in the treatment of older patients (≥ 65 years), it is important to set the optimal dose of digoxin to prevent toxicity and therapeutic drug monitoring of digoxin trough plasmatic concentration (C0) may be useful., Aim: To assess measured C0, to evaluate age influence on digoxin pharmacokinetic parameters and to report adverse events in patients administered digoxin., Methods: It consisted in a retrospective study. We included all the patients addressed to the department of clinical pharmacology for digoxin C0 measurement by an automated fluorescence polarization immunoassay. Therapeutic ranges of digoxin C0 were: 1 to 2.5 ng.mL-1 in children, 0.8 to 2 ng.mL-1 in adults and 0.5 to 0.9 ng.mL-1 in older adults (≥ 65 years) in atrial fibrillation and heart failure., Results: We collected 183 samples from 132 patients. Sex ratio M/W was 0.47. Mean age was 60 years and 57% of patients were older adults. Mean dose of digoxin was 0.3 mg.day-1. In older adults, 45% were administered daily doses over 0.125 mg.day-1. Mean digoxin C0 was 1.6 ng.mL-1. There was more supra-therapeutic C0 in older adults than younger ones (p<0.0001).There was no correlation between C0 and daily dose of digoxin. Adverse events, mainly cardiac and digestive, were reported in 47 patients (36%), among this population 47% were older adults., Conclusion: TDM is useful to prevent toxicity, mainly in older adults where diagnosis may be difficult to establish.

Introduction: Mycophenolic acid (MPA) requires routine therapeutic drug monitoring., Aim: To evaluate the suitability of a MPA Immunoassay CEDIA performed on Indiko® analyzer (Thermo fisher) for monitoring of MPA by comparing values obtained by HPLC-UV method., Methods: This study was carried out on 114 blood samples collected from renal transplant, using high performance liquid chromatography combined with ultraviolet detection (HPLC-UV, reference method) and the new immunoassay on CEDIA., Results: The assay was linear for a mycophenolic acid concentration up to 10 μg/mL. When MPA concentrations in all 114 transplant recipients obtained by the HPLC-UV (x-axis) method were compared with corresponding values obtained by the CEDIA® method (y-axis), the following regression equation was obtained: CEDIA® = 1.558 HPLC + 0.49 (r = 0.86). However more significant positive bias was observed (37 %)., Conclusion: The data presented suggest that the CEDIA® MPA immunoassay, run on the Indiko® analyzer, over-estimates plasma MPA concentrations. However, CEDIA® immunoassay is less laborious and time consuming than chromatographia techniques.

The use of cyclosporin in nephrotic syndrome can be considered in cortico-resistance or cortico-dependence. Cyclosporin is an immunosuppressant with a narrow therapeutic range and large pharmacokinetics variability justifying its therapeutic drug monitoring (TDM). The aim of this study was to evaluate the TDM of cyclosporin by the measurement of AUC0-12h in patients with nephrotic syndrome and to study the correlations between the AUC0-12h and the different blood concentrations of cyclosporin. It is a retrospective study from 2009 to 2016. TDM of cyclosporin was carrying out by ARCHITECT®. Determination of the AUC0-12h was made from three samples taken at T0, T60min and T180min obtained by a model of population pharmacokinetics of cyclosporin. A total of 20 patients were evaluated (29 abbreviated kinetics). The median AUC0-12h was 4.76 mg*h/L. Considering the target 5 mg*h/L during the first 6 months, 6 AUC0-12h were sub-therapeutic and 5 supra-therapeutic, no AUC0-12h was in the therapeutic range. Considering the 3 mg*h/L as a target during the following months, 13 AUC0-12h among 18 were supra-therapeutic. A correlation coefficient between the AUC0-12h of cyclosporin and C0 was 0.798. Correlation between AUC0-12h and C2h was 0.909. The median C2h found in our work was 878 ng / mL during the first six months versus 1039 ng / mL in the following months. Our patients are overexposed to cyclosporin and TDM of this drug by determination of AUC0-12h or by C2h would be more interesting than TDM by C0. TDM allows a better individual dose adjustment to avoid especially toxicity of cyclosporin.

Objective: In this study, we aimed to analyze the trough plasmatic levels (C0) of the antiepileptic drugs (AED) administered by nasogastric tubes (NGT) in comatose patients and to draw up recommendations for therapeutic drug monitoring (TDM) and for the modalities of AED administration by NGT., Methods: We conducted a retrospective study on comatose patients addressed over six years and 10 months in Clinical Pharmacology for C0 measurement of AED administered by NGT., Results: In this study, the sex-ratio was 2.38 (44 patients). The patients' median age was 24 years. There was 14.5% of children (≤16 years). Among the 103 samples, C0 measurement concerned valproic acid in 57%, phenobarbital in 28 % and carbamazepine in 15%. Two AED or more were associated in 42% of patients. AED were associated to other drugs in 85% of cases. The AED C0 were subtherapeutic in 71% of cases. C0/Dp lower than recommanded in 65 %. In these samples, 55% presented at least one drug association with the concerned AED. In 45% of the cases, there was no drug association but a non-respect of modalities of AED administration by NGT in patients., Conclusion:   The drug monitoring is a useful tool to assess drug-drug interactions and to control modalities of AED administration in comatose patients.

Ciclosporine (CsA) is an immunosuppressant drug used in bone marrow transplantation in order to extend allograft survival. Despite its efficiency, CsA can expose to therapeutic failure or to toxicity because of underdosing or overdosage. So, many techniques of monitoring CsA in blood were used, the referance one is the chromatographic technique then, the automated techniques: fluorescence polarization immunoassay (FPIA) and chimiluminescent microparticle immunoassay (CMIA). In this study, we aimed to compare the results of CsA concentrations measured by the two automised techniques. Statistical studies showed that the two techniques were repeatable and reproductible. Results obtained by FPIA were slightly higher than those obtained by CMIA but without a significative difference. In conclusion, FPIA technique could be used to measure CsA blood concentration in replacement of CMIA in case of technical problems.