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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: Carbamazepine could be used on monotherapy or associated to other antiepileptic drugs (AED). In these cases, drug interactions should be taken into account., Aim: To assess the influence of the coadministration of CBZ with other AED on the trough plasmatic concentration (C0) of CBZ in epileptic adults., Methods: We performed a retrospective study over a period of 9 years in the Department of Clinical Pharmacology in the Tunisian National Centre "Chalbi Belkahia" of Pharmacovigilance. Our study included samples from adult patients receiving CBZ alone or associated to other AED for epilepsy. Trough plasma CBZ plasma concentrations were measured by an immunological method. Included samples were divided in four groups: i/ group 1 (G1) receiving CBZ as monotherapy, ii/ group 2 (G2) treated by CBZ with an enzyme inducer (phenobarbital or phenytoin), iii/ group 3 (G3) taking CBZ associated to an enzyme inhibitor (valproic acid (VPA)), iv/ group 4 (G4), treated by CBZ associated to enzyme inducer (phenobarbital or phenytoin) and enzyme inhibitor (valproic acid) at the same time., Results: There were no significant differences between different groups in age, weight and sex ratio. However statistical analysis showed a significant decrease in C0/D CBZ ratio between G1 and G2 and between G1 and G4 (p<0.001). However, the difference was not significant between G1 and G3 (p=1.2044)., Conclusion: It is important to check and to prevent the consequences of the interaction between CBZ and other AED in order to avoid inefficiency and toxicity.

Background: Paclitaxel (PTX) is an anticancer drug used in the treatment of many cancer , alone or in combination with other anti-tumors. It has a narrow therapeutic range, a large inter and intra-individual pharmacokinetic variability and haematological toxicity. The most effective pharmacokinetic parameter seems to be the time during which the plasma concentration is over 0.05 μmol/L., Aim: To develop and validate a new method for PTX quantitation in plasma using HPLC with UV/visible detection., Methods: A rapid HPLC-UV method was developed for the determination of PTX level in plasma. All solvents used were HPLC grade., Results: After liquid-liquid extraction, chromatographic separation was achieved using an RP 18 (250 mm) column. The mobile phase was composed of acetonitrile and 0.1 M potassium dihyrogenophosphate (49/51) (v/v). Clonazepam was used as internal standard. This technique was linear over the range 50 ng/mL to 1500 ng/mL (r= 0.998). The evaluation of precision showed that our method is repeatable with a within-day coefficient of variation (CV) ranging from 6.94 to 18.78 % and reproducible for three studied concentrations low, medium and high with day-to-day CV of 14.92, 10.46 and 11.8% respectively. Under these conditions, each analysis required no longer than 12.81 min., Conclusion: We have developed and validate a new assay for PTX monitoring using HPLC with UV detection which is sensible, specific, reliable and easy to carry out in clinical use for its therapeutic drug monitoring.

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.

Drug interactions are unavoidable and need to be proactively identified and managed, in particular, the inductive effect of rifampin on tacrolimus whose potency and duration data are limited. We report the case of a renal transplant patient who was prescribed tacrolimus with preserved tough blood levels (C0) of 7.9 +/- 2 ng/mL. He presented ganglionic tuberculosis and started rifampin. One day later, C0 was 2.6 ng/mL with 5 mg/day. The serum creatinin was normal. Nine days later, C0 was 1.6 ng/mL with 7 mg/day. In this case-report, the tacrolimus-rifampin interaction occurred just one day after rifampin introduction necessitating early C0 monitoring.

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.