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Background While the concept of medication reconciliation seems relatively straightforward, implementing medication reconciliation has proved to be complex and challenging. In our setting, a teaching hospital with 700 beds, it seems very hard to perform extensive and complete reconciliation for every patient. Purpose The objectives of this study were to describe the frequency and type of medication discrepancies (MD) during admission in cardiology, and to identify patients with a high risk of unintended medication discrepancies (UMD). Material and methods Medication reconciliation was conducted at admission in the cardiology department over 4 weeks by trained pharmacists. (1) The best possible medication history (BPMH) was obtained using multiple sources (interview with the patient/family member, prescription vials, medication list, contact with general practitioner and community pharmacy, medical and pharmaceutical files). (2) Comparison of BPMH with the initial hospital prescription, identification of MD. (3) Classification of MD (intended/unintended) with the physician. Tools have been tested and validated in a pilot study. Statistical analysis examined the associations between UMD and patient reported factors (performed using R software). Statistical significance was reached if p Results During the study period, 100 patients were included, mean age 67.6 years (SD 17.7), sex ratio (M/F) 1.3, corresponding to 746 prescription lines. Overall, 544 MD were identified, including 77 UMD (42% of patients). The most common UMD was omission (70%). Do not speak French (p=0.007), to be admitted to a hospitalisation unit (compared with intensive care unit) (p=0.019), a low level of education (p=0.004), ≥2 comorbidities (p=0.001), long term illness (p=0.042) and ≥8 drugs in the initial prescription (p=0.004) were found to be significantly associated with UMD. Level of education remained significantly and independently associated with UMD after adjusting in the multivariate analysis for factors statistically significant in the univariate analysis. Conclusion Our study allowed us to identify predicting factors for UMD. Selection of patients for medication reconciliation must take into consideration factors that have been statistically identified, but are also practical. It is difficult to obtain information about level of education. Therefore, we decided to prioritise patients with ≥ 8 drugs in the initial prescription for medication reconciliation. No conflict of interest

Background In January 2013, a multidisciplinary educational programme, ‘ETAP’, for patients treated with oral anticoagulants was implemented in our cardiology department. Purpose To evaluate skills and adherence regarding anticoagulant therapy of patients included in an educational programme. To examine factors associated with poor skills scores. Material and methods Patients were enrolled in the ETAP programme and received individual education from a multidisciplinary team (dietician, nurse and pharmacist) from January 2013 to February 2016, and those who gave their oral consent were included in this assessment. During hospitalisation, an initial evaluation skill score (E1 score: 0 to 1) was assessed with a specific questionnaire designed by our team. At least 1 month after the educational intervention and discharge from the hospital, patients were called by a trained pharmacy student. Patients were submitted to the same skill questionnaire (E2 score: 0 to 1) and an 8 item Morisky medication adherence scale (MMAS-8). Furthermore, patients were interrogated on the occurrence of haemorrhagic or thrombotic events and INR value at the time of the call. Results 412 patients were enrolled in ETAP. 27% (365/1336) of patients receiving VKA and 16% (47/286) of patients receiving DOA were educated. Mean skill scores were 0.82 (±0.23) points and 0.81 (±0.18) points for E1 and E2, respectively, and no significant difference (p=0.47) was observed the two. 66% of patients had high level of adherence. Thrombotic and haemorrhagic events were observed in 11% (18/161) of interviewed patients. 58% (93/161) of patients were aware of their INR, and INR was in the target area. The skill score declined with age (p Conclusion Only 16% of patients receiving DOA were educated; most patients did not start DAO treatment in our department and VKA patients were favoured. As the mean E2 skill score assessed was not significantly different from the mean E1 score, patients seem to keep their skills in the long term. 44% of patient had a poor level of adherence. This study underlines the necessity to improve education in elderly patients and in patients treated by DOA. No conflict of interest

To assess the impact of physician awareness to promote the prescription and the dispensing of generic drugs at hospital discharge.The study consisted in a Before/After Study design including the analysis of medical prescriptions at hospital discharge, after a pharmaceutical intervention to physicians in a geriatric ward. Each drug was classified according to its terms of prescribing (International Nonproprietary Name (INN), Generic or Trade Name). The primary endpoint defined is the rate of medication prescribed by INN or generic. Statistical analysis was performed on all medicines and according to the prescribers' status (junior/senior).Three hundred and fifty one drugs were prescribed in the group "before intervention" versus 301 in the group "after". The average number of drugs prescribed per patient was similar between the two groups (9.5 drugs/patient). A generic prescription has been improved by 5% between the two periods (19.7% "before" vs 24.3% "after", p=0.27). Analysis on prescriber status indicates that the pharmaceutical intervention had a significant impact on junior physicians, which resulted in improved prescribing of drug (INN or generic) from 17.6% to 31.4% between the two periods (p=0.006).The pharmaceutical intervention to physicians has led to an improvement of drug prescription (INN or generic) at hospital discharge. This awareness has affected mainly junior prescribers hence the need to extend this type of intervention to all prescribers of our establishment.

Immunosuppressive (IS) drugs are now widely used as preventive treatments of allograft rejection in transplantation. Therapeutic drug monitoring (TDM) using trough whole blood concentrations is usually warranted and therapeutic range is recommended to ensure efficacy and prevent toxicity from these drugs. This intensive TDM reduces acute graft rejection but despite this management, the acute rejection rate still remains high in the first two years post-transplantation and few improvements have been made recently to reduce this rate. Moreover, in some patients, acute rejections occur despite adequate trough whole blood IS concentrations. Thus, other ways to monitor immunosuppressive drug effects have to be investigated. As lymphocyte cells are the site of action of IS drugs and so the effect compartment of the drug, monitoring IS drugs in lymphocytes, or for practical reasons in peripheral blood mononuclear cells (PBMC), could be more relevant than standard TDM. The aim of this paper is to review the recent work conducted on the advantages of monitoring IS drugs in PBMC, particularly for calcineurin inhibitors and mammalian target of rapamycin (m-TOR) inhibitors, from an analytical point of view as well as a clinical point of view.

We read with great interest the article by Wirtz et al,1 which presents an overview on access to cardiovascular medications in low- and middle-income countries. It is noteworthy that, among the 5 health system dimensions of access described, the first 4 have been well researched through large multination studies. Low availabilit y of cardiovascular disease medicines has been well reported; a fairly recent meta-analysis of surveys from 36 countries assessed access to different classes of cardiovascular medicines.1 Several peer-reviewed publications have also reported on the affordability of cardiovascular …

International audience; BackgroundOral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers’ perceptions of what patients should know, rather than on patients’ preferences.ObjectiveTo investigate patients’ viewpoints on educational needs and preferred modalities of information delivery.MethodsWe conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France.ResultsOf the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30–2.46). Pharmacists (1.69, 1.58–1.80), nurses (1.05, 0.95–1.16), and patient associations (0.36, 0.29–0.44), along with group sessions (0.85, 0.75–0.95), the internet (0.77, 0.67–0.88), and delivery of material at the patient’s home (1.26, 1.14–1.38), were ranked poorly in terms of delivering educational material.ConclusionThis study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their effectiveness.

BACKGROUND The aim of this study was, using routine drug monitoring data, to identify patient characteristics that may influence everolimus (EVE) pharmacokinetic parameters and to develop a population pharmacokinetic model to predict EVE whole blood concentrations in cardiac recipients. METHODS Fifty-nine patients were enrolled in the prospective study. Patient's characteristics were recorded including biological covariates and treatments. CYP3A5 and ABCB1 polymorphisms were determined. Seven hundred seventy-five EVE blood samples were collected for routine drug monitoring. Population pharmacokinetic modeling was carried out using the nonlinear mixed-effects modeling program. Results were analyzed according to a 1-compartment pharmacokinetic model with linear absorption and elimination. The model was evaluated using a bootstrap method and a visual predictive check procedure. RESULTS The pharmacokinetic of EVE in cardiac recipients was best described by a 1-compartment model. Interindividual variability was best described by an exponential error model and residual error by a proportional plus additive error model. Estimation of EVE apparent clearance (3.33 ± 0.20 L/h) and apparent volume of distribution (146 ± 33 L) were in accordance with previously published data. Bilirubinemia and cyclosporine significantly influenced EVE clearance. Some covariates that were expected to influence EVE clearance, for example, ABCB1 and CYP3A5 polymorphisms, were not evidenced. No covariates influenced the volume of distribution of EVE. CONCLUSIONS This study is the first population pharmacokinetic model of EVE in heart transplantation patients. It allows a better description of the pharmacokinetics of EVE. The present population pharmacokinetic model allows estimating a priori and a posteriori EVE concentrations in cardiac recipients and could limit the over and under drug exposure in this population.

A reliable ultra high performance liquid chromatography tandem mass spectrometry method has been developed for the determination of everolimus in human peripheral blood mononuclear cells (PBMCs). Protein precipitation was used for sample preparation. Analysis was performed on an UPLC Waters Acquity system. Chromatography was carried out using a cartridge column MassTrak TDM C18 (2.1×10 mm) with 0.1% formic acid and 2 mM of ammonium acetate in water and 0.1% formic acid and 2mM of ammonium acetate in methanol mixture as a mobile phase delivered at a flow rate of 0.4 mL/min in gradient mode. The assay was linear over a range of 0-12.5 ng/mL. The analysis of quality control samples at 2.5, 5.0 and 10.0 ng/mL demonstrated good precision with relative standard deviation of less than 15%. Recoveries at concentrations of 2.5, 5.0 and 10.0 ng/mL were all greater than 83%. The method was successfully applied to the analysis of everolimus in PBMCs from blood samples of transplant recipients.

The use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. We have previously described a tacrolimus population pharmacokinetics model obtained in an adult kidney transplant cohort. The aims of the present study were (1) to validate that model using an external dataset and (2) to evaluate the prediction using a Bayesian method. Data were retrospectively collected from 34 adult patients receiving kidney transplantation. Trough blood concentrations of tacrolimus were predicted using the empirical Bayesian method with sparse samples obtained during the previous week. The system performance was evaluated by the mean prediction error (ME), mean absolute prediction error (MAE). and root mean square error (RMSE). Patients were administrated oral or intravenous tacrolimus as part of a triple immunosuppressive regimen with mycophenolate mofetil and corticosteroids. Subsequent doses were adjusted on the basis of clinical evidence of efficacy and toxicity and by routine therapeutic drug monitoring. In our previous model, clearance increased with post transplantation days and with prednisone dosage. Concentrations predicted by the population mean pharmacokinetic parameter values match well with observed concentrations during oral therapy. Bayesian prediction using trough concentrations obtained after 21 days of treatment significantly decreased ME, MAE, and RMSE compared with predictions from data including this period. After 21 days of treatment, there was an insignificant bias ME (0.22 ± 2.59 ng/ml), a reasonable precision MAE (1.97 ± 1.69 ng/ml) and RMSE (1.28 ± 0.58 ng/ml). The present study demonstrates the suitability of the Bayesian method for the prediction of trough blood concentrations of tacrolimus using only few samples in adult kidney transplantation recipients.

International audience; ObjectivesDespite improvements in patient management and extensive use of therapeutic drug monitoring (TDM), the rate of acute cellular rejection (ACR) remains high in patients treated with tacrolimus (TAC). Moreover, some patients experienced ACR while their whole-blood (WB) concentrations were maintained within the therapeutic range meaning that TDM in WB misrepresents the drug effect. Thus, monitoring TAC directly inside of its effect compartment (intracellular concentrations) or monitoring directly the inhibitory effect on the target protein (calcineurin activity) could be more relevant. The aim of the present study was to explore, in 10 de novo liver transplant recipients, the relationship between TAC whole-blood concentrations, TAC intracellular concentrations and TAC-induced intracellular calcineurin inhibition at day 1 and day 7 after treatment initiation.Design and methodsProspective monocentric observational pharmacokinetic (WB and intracellular concentrations)–pharmacodynamic (calcineurin activity) study.ResultsFull intracellular TAC pharmacokinetic as well as calcineurin activity steady-state profiles is presented in the study. The main result of this study is the lack of relationship between TAC pharmacokinetics (WB and leukocytes) and calcineurin activity in leukocytes at day 1 and day 7 after the graft implantation.ConclusionsDrug monitoring of TAC intracellular concentrations and determination of the calcineurin activity are among future potential biomarkers of acute rejection in transplant recipients. A better knowledge of the relationship between TAC whole blood and intracellular concentrations and calcineurin activity appears necessary before planning clinical trials to evaluate their potential interest as predictive biomarkers.

A comparison of the oxidations of diclofenac with microsomes of yeasts expressing various human liver cytochromes P450 showed that P450 2C9 regioselectively led to 4'-hydroxy diclofenac (4'-OHD) whereas P450 3A4 only led to 5-hydroxy diclofenac (5-OHD). P450 2C19, 2C18, and 2C8 led to the simultaneous formation of 4'-OHD and 5-OHD (respective molar ratios of 1.3, 0.37, and 0.17), and P450 1A1, 1A2, 2D6, and 2E1 failed to give any detectable hydroxylated metabolite under identical conditions. P450 2C9 was found to be much more efficient for diclofenac hydroxylation than all the other P450s tested (k(cat)/K(M) of 1.6 min(-1) microM(-1) instead of 0.025 for the second more active P450), mainly because of markedly lower K(M) values (15 +/- 8 instead of values between 170 and 630 microM). Oxidation of diclofenac with chemical model systems of cytochrome P450 based on iron porphyrin catalysts exclusively led to the quinone imine derived from two-electron oxidation of 5-OHD, in an almost quantitative yield. Two derivatives of diclofenac lacking its COO(-) function were then synthesized; their oxidation by recombinant human P450 2Cs always led to a major product coming from their 5-hydroxylation. Substrate 2, which derives from reduction of the COO(-) function of diclofenac to the CH(2)OH function, was studied in more detail. All the P450s tested (1A1, 1A2, 2C8, 2C9, 2C18, 2C19, 2D6, and 3A4) almost exclusively led to its 5-hydroxylation. P450s of the 2C subfamily were found to be the most efficient catalysts for this reaction, with k(cat)/K(M) values between 0.2 and 1.6 min(-1) microM(-1). Oxidation of 2 with an iron porphyrin-based chemical model of cytochrome P450 also led to a product derived from the oxidation of 2 at position 5. These results show that oxidation of diclofenac and its derivative 2, either with chemical model systems of cytochrome P450 or with recombinant human P450s, generally occurs at position 5. This position, para to the NH group on the more electron-rich aromatic ring of diclofenac derivatives, is thus, as expected, the privileged site of reaction of electrophilic, oxidant species. The most spectacular exception to this chemoselective 5-oxidation of diclofenac derivatives was found for oxidation of diclofenac itself with P450 2C9 (and P450 2C19 and 2C18 to a lesser extent), which only led to 4'-OHD. A likely explanation for this result is a strict positioning of diclofenac in the P450 2C9 active site, via its COO(-) function, to completely orientate its hydroxylation toward position 4', which is not chemically preferred. P450 2C19, 2C18, and 2C8 would not lead to such a strict positioning as they give mixtures of 4'-OHD and 5-OHD. The above results show that diclofenac derivatives are interesting tools to compare the active site topologies of human P450 2Cs.

International audience; OBJECTIVES: Despite the intensive therapeutic drug monitoring of tacrolimus (TAC) using trough whole blood concentrations, graft rejections occur in transplant recipient patients. Thus, other ways to monitor closely immunosuppressive treatments are necessary. A promising way of monitoring TAC treatments could be the measure of its concentrations inside of the lymphocyte cell. Whereas the pharmacokinetics of TAC in peripheral blood mononuclear cells (PBMCs) was evaluated in renal and liver transplant recipients, data regarding PBMC concentrations of TAC in cardiac transplant recipients are lacking. This study aimed, in cardiac transplant recipients: to validate a method for determination of TAC in PBMC, to investigate PBMC trough concentrations of TAC, and to evaluate their relationship with trough whole blood concentrations. DESIGN AND METHOD: We developed and validated a High-performance-liquid-chromatography tandem mass-spectrometry method of TAC quantitation in PBMC. The method was then evaluated by determining TAC concentrations in PBMC of 24 cardiac transplant recipients. RESULTS: Twenty-four patients were prospectively included in the study. Tacrolimus PBMC concentrations displayed a large inter-individual pharmacokinetic variability (CV=71.4%) in the cohort. A lack of correlation between TAC whole blood trough concentrations and TAC trough concentrations in PBMCs was found (r=0.259; p=0.183). CONCLUSION: Further studies should be implemented to evaluate the correlation between TAC concentrations in PBMC and clinical outcomes in cardiac transplant recipients to allow concluding whether monitoring TAC concentrations in PBMC is a good tool to prevent graft rejection in cardiac recipients.

The neuraminidase inhibitor oseltamivir is a recommended treatment for influenza A (H1N1) infection. In rare cases, some patients develop influenza-associated multiple organ failures, requiring rescue therapies such as extracorporeal membrane oxygenation (ECMO) or continuous venovenous hemodiafiltration (CVVHDF). This study was designed to evaluate the impact of ECMO and CVVHDF on the pharmacokinetics of oseltamivir carboxylate (OC) in critically ill patients with pandemic (H1N1) influenza treated with oseltamivir.Seven critically ill patients on venovenous ECMO for severe pandemic (H1N1) influenza associated with acute respiratory distress syndrome were treated with various doses of oseltamivir (75 or 150 mg twice daily). Because of acute kidney injury, 3 of them also received CVVHDF. OC, the active form of oseltamivir, was quantified in plasma, and main pharmacokinetic parameters were determined.OC Cmax (1029 ± 478 ng/mL) and area under the curve (9.00 ± 4.52 mcg·h/mL) for patients on ECMO with preserved renal function were comparable with those of healthy volunteers or noncritically ill patients. Patients both on ECMO and CVVHDF had 4-to 5-fold higher OC Cmax and area under the curve.ECMO by itself did not impact on the pharmacokinetics of OC. However, the drug accumulated in the plasma of patients on ECMO who also received CVVHDF for renal failure. Based on these results, we recommend that oseltamivir dosage should be decreased and plasma levels of OC be monitored in patients receiving CVVHDF because of acute kidney injury.

The use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. Tacrolimus population pharmacokinetics, including bioavailability, were investigated in an adult kidney transplant cohort to identify patient characteristics that influence pharmacokinetics.The database (drug monitoring data) included 83 adult kidney transplant recipients and analysis was performed by a population approach with NONMEM. Data were collected during the first months after transplantation. Patients were administered oral or intravenous tacrolimus as part of a triple immunosuppressive regimen that also included mycophenolate mofetil and corticosteroids. Subsequent doses were adjusted on the basis of clinical evidence of efficacy and toxicity as in routine therapeutic drug monitoring.A one compartment open model with linear absorption and elimination adequately described the data. The typical value of minimal clearance was 1.8 +/- 0.2 l h(-1). Clearance increased with time post transplantation to reach 50% of maximal value after 3.8 +/- 0.5 days, with a maximal value of 5.6 l h(-1). Moreover clearance increased by approximately 1.6 fold (range 0.5-1.6) if the dose of prednisone was25 mg. The typical value for volume of distribution, V, (98 +/- 13 l kg(-1)) was similar to reported values in kidney transplant patients. The oral bioavailability of tacrolimus was poor and ranged from 11.2 to 19.1%. No covariates significantly influenced V or F.The number of days postoperation and corticosteroid dose were significant covariates influencing tacrolimus clearance.

What is already known about this subject • In spite of its success in ensuring graft survival, therapeutic use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. • Some studies of population pharmacokinetics have already been conducted in liver transplant recipients and in paediatric patients. What this study adds • Our work determined population pharmacokinetic parameters, in particular bioavailability, in kidney transplant recipients and the relative importance of factors influencing the disposition of tacrolimus. • Clearance was modelled and days postoperation and corticosteroids dose were significant covariates. Aims The use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. Tacrolimus population pharmacokinetics, including bioavailability, were investigated in an adult kidney transplant cohort to identify patient characteristics that influence pharmacokinetics. Methods The database (drug monitoring data) included 83 adult kidney transplant recipients and analysis was performed by a population approach with NONMEM. Data were collected during the first months after transplantation. Patients were administered oral or intravenous tacrolimus as part of a triple immunosuppressive regimen that also included mycophenolate mofetil and corticosteroids. Subsequent doses were adjusted on the basis of clinical evidence of efficacy and toxicity as in routine therapeutic drug monitoring. Results A one compartment open model with linear absorption and elimination adequately described the data. The typical value of minimal clearance was 1.8 ± 0.2 l h−1. Clearance increased with time post transplantation to reach 50% of maximal value after 3.8 ± 0.5 days, with a maximal value of 5.6 l h−1. Moreover clearance increased by approximately 1.6 fold (range 0.5–1.6) if the dose of prednisone was >25 mg. The typical value for volume of distribution, V, (98 ± 13 l kg−1) was similar to reported values in kidney transplant patients. The oral bioavailability of tacrolimus was poor and ranged from 11.2 to 19.1%. No covariates significantly influenced V or F. Conclusions The number of days postoperation and corticosteroid dose were significant covariates influencing tacrolimus clearance.

Background In January 2013, an education program for patients treated with oral anticoagulants called “ ETAP ” was implemented in the cardiology department of our hospital. The day after the educational intervention, patient knowledge and coping are assessed but long-term knowledge, coping and medicines adherence have never been investigated up to now. Purpose To assess long-term knowledge, coping and adherence of patients enrolled in ETAP since January 2013. Material and methods 1) January 2013–August 2014 : During hospitalisation, an initial “knowledge and coping score” (E1 score: 0 to 10 points) was awarded for patients enrolled in the education program with a specific questionnaire designed by the ETAP team. 2) June–September 2014 : At least one month after discharge from the hospital, a pharmacy student called every patient at home who had given his verbal consent beforehand. A long-term “knowledge and coping score” (E2 score) was awarded with the same questionnaire. Medicines adherence was calculated with the 8-item Morisky Medication Adherence Scale (MMAS-8). Results Of the 236 patients contacted, 100 patients completed the study. Mean “knowledge and coping scores” were both above 8 points (E1: 8.61 ± 2.36, E2: 8.23 ± 2.03). No significant difference (p = 0.35) was observed between means of E1 and E2 scores. MMAS-8 showed that most patients (70%) had a high level of adherence. No correlation was observed between E1 or E2 scores and adherence. Conclusion The results of this pilot study suggest that most patients retain their long-term knowledge and coping skills. These data are in agreement with other studies. 1 The medicines adherence to oral anticoagulants estimated by MMAS-8 was higher than in routine practice. Assessment of the ETAP program should be improved by including biological and clinical outcomes such as INR or bleeding events collection. Reference Thiriat N, et al . Therapeutic education of elderly patients under antivitamin - K treatment: evaluation of the program after 5 years. J Pharm Belg 2014;(3):30–7 No conflict of interest.

To investigate the population pharmacokinetics of tacrolimus in an adult liver transplant cohort using routine drug monitoring data and to identify patient characteristics that influence pharmacokinetic parameters.Tacrolimus pharmacokinetics was studied in 37 adult patients using a population approach performed with NONMEM.A one-compartment open model with linear absorption and elimination adequately described the data. The apparent clearance (CL) was approximately zero in the immediate post-operative days (PODs) and then rapidly increased as a function of POD to reach a plateau. This was modelled as a sigmoid relationship with the characteristic parameters CL(max) (plateau), TCL(50) (time to obtain 50% of the plateau) and gamma (coefficient of sigmoidicity). This clearance model was thought to describe the hepatic function regeneration after transplantation. Typical population estimates (percentage inter-individual variability) of CL(max), TCL50, and gamma and apparent distribution volumes (V) were 36 l/h (43%), 6.3 days (33%), and 4.9 l and 1870 l (49%), respectively. The CL(max) was negatively related to plasma albumin, and TCL50 was positively related to aspartate amino transferase (ASAT). Bayesian estimations performed at different POD times indicated that acceptable precisions in individual pharmacokinetic predictions could be obtained after the 15th POD.Tacrolimus clearance modelling showed that there was a large variation in individual CL estimates up to the 15th day post-surgery. After this period, the mean error resulting from the Bayesian estimation was strongly decreased and this estimation method could be applicable and should limit tacrolimus monitoring.

Introduction – objectifs En 2011, le comite des medicaments anti-infectieux a mis en place une dispensation controlee (DC) de 7 antibiotiques (ATB) dont les carbapenemes . La reevaluation de la prescription par un senior apres 72 h etait un critere prioritaire de la validation pharmaceutique. Ce travail a pour objectif principal d’etudier l’evolution de ce critere entre 2011 et 2013. Materiels et methodes Huit analyses de 1 mois ont ete realisees entre 2011 et 2013. Ont ete recueillis d’apres chaque ordonnance, la fonction du prescripteur (interne ou senior), et a partir de mi-2013, le contexte de l’infection, l’adaptation de la posologie a la fonction renale et les interventions pharmaceutiques (IP). Resultats La reevaluation des prescriptions par un senior a 72 h a regulierement augmente : 69 % en 2011 (315/453 ordonnances), 65 % en 2012 (346/531) et 89 % en 2013 (674/754). L’adaptation de la posologie a la fonction renale a evolue de 87 % mi-2013 (141/162) a 94 % (207/220) fin 2013. A partir de mi- 2013, le renforcement des IP a permis d’obtenir un taux de reevaluation par les seniors de 97 % (567/585) et un taux d’adaptation a la fonction renale de 99 % (578/585). Lors des 2 dernieres etudes, les taux de prescriptions probabilistes et documentees etaient respectivement de 46 % (63/137) et 19 % (26/137) pour les initiations et de 37 % (90/242) et 21 % (52/242) lors de la reevaluation. Conclusion Apres 72 h, la part des prises en charge probabilistes diminue, la reevaluation des traitements ATB s’avere indispensable. La mise en place de la dispensation controlee et le renforcement des interventions pharmaceutiques ont permis d’ameliorer non seulement la reevaluation par les seniors des prescriptions d’ATB, mais aussi l’adaptation de la posologie a la fonction renale.

Background The emergence of multiresistant bacteria and their spread has become a public health issue. In 2011, the Anti-Infective Drugs Committee of Saint Antoine Hospital (Paris) established a requirement for a specific prescription for 7 antibiotics (imipenem, doripenem, ertapenem, meropenem, linezolid, tigecycline and daptomycin) in order to restrain the use of these antibiotics. The Committee specially insists on the importance of the antibiotic treatment being reassessed after 72 h by a senior physician or an anti-infectious authority. Purpose To assess prescription quality and the contribution of a pharmaceutical intervention. Materials and methods Saint Antoine is a teaching hospital of 760 beds with surgical and medical units including a haematological department. In order to assess the quality of antibiotics prescriptions, two one-month surveys were carried out before and after a pharmaceutical intervention. During these periods, antibiotics prescriptions were exhaustively analysed and data were collected within an Excel table. The intervention: Informed clinical units in writing of the results of the first survey and the wish to improve them. Established pharmaceutical validation: each prescription was analysed by a pharmacist and if needed, he would require modifications. In the second survey, in order to assess whether the improvement in the quality of the prescriptions was attributable to the prescribers’ involvement or to the pharmaceutical validation, we collected data before and after modifications required by the pharmacist. Prescription quality was assessed by 5 criteria: Was the indication filled in? Did the physician provide information about initiation or continuation of the treatment? Was the treatment reassessed by a senior physician after 72 h? Was the serum creatinine entered by the physician? Was drug dose appropriate? Results Results are detailed in the following table: Conclusions The pharmacist’s intervention and physician’s involvement have improved the quality of prescriptions; results have undoubtedly improved between the two surveys. Every antibiotic prescription is henceforth systematically validated by a pharmacist. The next step is to establish a multidisciplinary cell to validate the indication. No conflict of interest.