Therapeutic Drug Monitoring In Practice Research Articles

Fast simultaneous LC/MS/MS determination of 10 active compounds in human serum for therapeutic drug monitoring in psychiatric medication.

A UPLC/MS/MS method with simple protein precipitation has been validated for the fast simultaneous analysis of agomelatine, asenapine, amisulpride, iloperidone, zotepine, melperone, ziprasidone, vilazodone, aripiprazole and its metabolite dehydro-aripiprazole in human serum. Alprenolol was applied as an internal standard. A BEH C18 (2.1 × 50 mm, 1.7 µm) column provided chromatographic separation of analytes using a binary mobile phase gradient (A, 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B, 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Mass spectrometric detection was performed in the positive electrospray ionization mode and ion suppression owing to matrix effects was evaluated. The validation criteria were determined: linearity, precision, accuracy, recovery, limit of detection, limit of quantification, reproducibility and matrix effect. The concentration range was as follows: 0.25-1000 ng/mL for agomelatine; 0.25-100 ng/mL for asenapine and iloperidone; 2.5-1000 ng/mL for amisulpride, aripiprazole, vilazodone and zotepine; 2.3-924.6 ng/mL for dehydroaripiprazole; 2.2-878.4 ng/mL for melperone; and 2.2-883.5 ng/mL for ziprasidone. Limits of quantitation below a therapeutic reference range were achieved for all analytes. Intra-run precision of 0.4-5.5 %, inter-run precision of 0.6-8.2% and overall recovery of 87.9-114.1% were obtained. The validated method was successfully implemented into routine practice for therapeutic drug monitoring in our hospital.

PTH-090 Laboratory experience of anti-tnf drug monitoring in routine practice – perspective from the first uk centre: Abstract PTH-090 Table 1

<h3>Introduction</h3> Therapeutic drug monitoring (TDM) of Infliximab (IFX) and Adalimumab (ADAL) has been in use in our centre since 2012. Here we present the TDM experience of our laboratory service at Viapath, St Thomas’ Hospital. <h3>Method</h3> Anti-TNF requests received between June 2012 and January 2015 were reviewed. All assays were performed using LISA-TRACKER Duo kits automated on eRobot (Theradiag, France). These assays measure free drug and anti-drug antibody (ADAb) and therefore inhibition studies were performed on samples with detectable drug levels (&gt;1 ug/ml) and positive ADAb. Results were classified according to drug levels (DL) and ADAb status. <h3>Results</h3> The laboratory analysed 2424 (17% internal) samples for IFX (Median DL 3.8 ug/mL, IQR 1.2–6.3) and 1335 (21% internal) samples for ADAL (Median DL 5.2 ug/mL, IQR 3.4–7.3) from IBD patients. Prevalence of detectable antibodies was higher in IFX (10%) than ADAL (4.1%) samples. External requests originated from &gt;90 different hospitals. Number of requests received for both assays doubled from 2013 to 2014 with batch frequency consequently decreasing from fortnightly to weekly. 40 patients had IFX &gt;1 ug/ml and were antibody positive. 16 of these patients were confirmed to have switched to ADAL due to loss of response to IFX therapy. Detectable DL observed in these cases was due to cross reactivity of ADAL with the IFX assay. 11 patients had false positive drug levels and 4 patients had borderline antibodies due to non specific binding. 1 patient had sample collected around infusion. 4 patients had subtherapeutic ADAL (1.1–1.4 ug/ml) and were antibody positive. 1 of these patients was confirmed to have switched to IFX due to loss of response to ADAL therapy. Detectable DL observed in this case was due to cross reactivity of IFX with the ADAL assay. 3 patients had false positive results for ADAL. From the data, it was evident that some centres monitored patients with serial measurements and made subsequent changes to therapy. 63 patients (IFX) and 52 patients (ADAL) had an average of 7 and 3 repeat measurements taken respectively. <h3>Conclusion</h3> Anti-TNF testing has been embedded in several IBD centres as a way of optimising therapy however variation in TDM practices was observed highlighting the need for national guidance. Significant increase in test requesting suggests assay based treatment strategies combined with clinical assessment is now an accepted practice in IBD. <h3>Disclosure of interest</h3> Z. Arkir: None Declared, N. Unsworth: None Declared, G. Richards: None Declared, Z. Odho: None Declared, P. Irving Speaker Bureau of: MSD, Abbvie and Takeda.

AN AUDIT OF THERAPEUTIC DRUG MONITORING IN PAEDIATRIC PATIENTS

Aim To investigate whether the current practice of therapeutic drug monitoring (TDM) within a large paediatric hospital adheres to hospital guidelines with respect to initial drug dosing, timing of assay, documentation of TDM assay and action taken as a consequence of the assay result. Method Drugs requiring TDM were identified from guidelines within the hospital formulary. Inpatients prescribed a TDM drug were identified by ward pharmacists during a six-week period in Oct-Nov 2013. Data was retrieved from each patient9s drug chart, medical notes and electronic patient record and recorded on a standard data collection form. The data collected included: patient details, TDM drug(s) prescribed, initial drug dose, time assay conducted, whether assay result was documented and any action taken. The data was analysed to determine whether each dose, the time of each assay and each action taken was in accordance with hospital guidelines. Statistical analysis was conducted to determine the extent of guideline adherence. Results Ten drugs requiring TDM were prescribed during the study period: dalteparin, digoxin, gentamicin, phenobarbital, phenytoin, sirolimus, tacrolimus, unfractionated heparin, vancomycin and warfarin. Sixty-five inpatients were prescribed at least one TDM drug and 192 TDM assays were conducted. Of the 67 TDM drugs that were initiated during the current admission, 55 (82.1%) were prescribed at the correct initial dose. It was found that 149/192 (77.6%) TDM assays were conducted at the correct time in relation to the time since initiation of treatment and the time since the previous dose. Results were documented in the medical notes or on the drug chart for 101/192 (52.6%) assays. Appropriate action (according to hospital guidelines) was taken following 149/192 (77.6%) assay results, although appropriateness could not be determined for tacrolimus, sirolimus and phenytoin (38/192; 19.8%) due to lack of guidance concerning what action should be taken following a non-therapeutic assay result. Conclusion The results showed that the current practice of TDM is largely in accordance with hospital guidelines. During the study period, most initial doses were prescribed correctly and most TDM assays were conducted at the correct time, although results were documented for only half the assays conducted. The findings did highlight limitations within the guidelines, particularly concerning action that should be taken when assay results for tacrolimus, sirolimus and phenytoin are non-therapeutic. In view of these findings, guideline development and improving documentation of assay results should be areas of focus. Future studies could investigate the effect of guideline adherence on drug efficacy or clinical outcome.

Can Pharmacometabolomics and LC-HRMS develop a new Concept for Therapeutic Drug Monitoring?

Therapeutic drug monitoring (TDM) is a concept for individualized drug dosing that was developed into clinical routine as a consequence of research findings on variable drug effects and analytical technology developments made in the 1950th and onwards, and founded the clinical pharmacology discipline (1,2). TDM in practice is about measuring a specific drug concentration in blood, serum or plasma, but may also include pharmacogenetic and pharmacodynamic investigations (3). For some time big hopes were put on pharmacogenetics to help explain inter-individual variability in drug response. It is now realized that variability may occur over time and relate to influences from both inborn as well as environmental factors, and that a more multifactorial approach is needed for complex biological systems (4). Examples of important use of TDM comprise treatment of epilepsy, infection, psychiatric disease and immunosuppression after transplantation (1,5,6). Analytical methods for TDM were using immunochemical, HPLC and GC techniques for long time, but this has recently, but slowly, been challenged by LC-MS techniques (7). One good example of this is methods for the immunosuppressive drugs tacrolimus, ciclosporin, sirolimus and everolimus (8,9). LC-MS methods have offered significant improvements in the quality of analytical method performance. It has been demonstrated that LC-MS offer improvement in accuracy, precision and cost-effectiveness, and also can be made robust. With the use of LC-MS in LC-tandem MS SRM mode multi-component methods can be constructed with unique combination of selectivity and sensitivity. Analytical method demands in TDM are set by the requirements of accuracy, cost-effectiveness, rapid reporting and robustness in a routine laboratory environment.

On the Slow Diffusion of Point-of-Care Systems in Therapeutic Drug Monitoring.

Recent advancements in point-of-care (PoC) technologies show great transformative promises for personalized preventative and predictive medicine. However, fields like therapeutic drug monitoring (TDM), that first allowed for personalized treatment of patients’ disease, still lag behind in the widespread application of PoC devices for monitoring of patients. Surprisingly, very few applications in commonly monitored drugs, such as anti-epileptics, are paving the way for a PoC approach to patient therapy monitoring compared to other fields like intensive care cardiac markers monitoring, glycemic controls in diabetes, or bench-top hematological parameters analysis at the local drug store. Such delay in the development of portable fast clinically effective drug monitoring devices is in our opinion due more to an inertial drag on the pervasiveness of these new devices into the clinical field than a lack of technical capability. At the same time, some very promising technologies failed in the clinical practice for inadequate understanding of the outcome parameters necessary for a relevant technological breakthrough that has superior clinical performance. We hope, by over-viewing both TDM practice and its yet unmet needs and latest advancement in micro- and nanotechnology applications to PoC clinical devices, to help bridging the two communities, the one exploiting analytical technologies and the one mastering the most advanced techniques, into translating existing and forthcoming technologies in effective devices.

How do we use therapeutic drug monitoring to improve outcomes from severe infections in critically ill patients?

High mortality and morbidity rates associated with severe infections in the critically ill continue to be a significant issue for the healthcare system. In view of the diverse and unique pharmacokinetic profile of drugs in this patient population, there is increasing use of therapeutic drug monitoring (TDM) in attempt to optimize the exposure of antibiotics, improve clinical outcome and minimize the emergence of antibiotic resistance. Despite this, a beneficial clinical outcome for TDM of antibiotics has only been demonstrated for aminoglycosides in a general hospital patient population. Clinical outcome studies for other antibiotics remain elusive. Further, there is significant variability among institutions with respect to the practice of TDM including the selection of patients, sampling time for concentration monitoring, methodologies of antibiotic assay, selection of PK/PD targets as well as dose optimisation strategies. The aim of this paper is to review the available evidence relating to practices of antibiotic TDM, and describe how TDM can be applied to potentially improve outcomes from severe infections in the critically ill.

Impact of Clinical Decision Support Guidelines on Therapeutic Drug Monitoring of Gentamicin in Newborns

Our institution's gentamicin dosing and therapeutic drug monitoring (TDM) practices for newborns were suspected to be very heterogeneous. Once-daily dosing (ODD) or extended-interval dosing (EID) and trough concentration measurement were recommended. Clinical decision support guidelines were developed and implemented as clinical decision support in the computerized prescriber order entry system. Impact on dosing, TDM practices, and blood sampling were evaluated. A 1-year retrospective historically controlled study before (April 2008-March 2009) and after the implementation of guidelines (January 2010-December 2010) for newborns (<30 days of life) receiving gentamicin. Blood concentrations (% of peak concentrations sampled, % of patients with zero or one concentration sampled, % of trough concentrations ≤1 mg/L) and dose regimen (ODD/EID) were compared between groups. Factors potentially associated with gentamicin concentration were analyzed (multivariate analysis). One hundred thirty-two (postguidelines) versus 102 (preguidelines) patients were included (median gestational age: 34.3 versus 35.8 weeks, P > 0.05). After implementation of the guidelines, an ODD/EID regimen was almost exclusively used (97.7% versus 61.6%, P < 0.001), the percentage of peak concentrations (0.9% versus 17.2%, P < 0.001) and the number of blood samples per patient (87.1% having 0 or 1 concentration measured versus 48.0, P < 0.001) sharply reduced. A significantly higher percentage of trough concentrations were ≤1 mg/L (68.5% versus 33.0%, P < 0.001). The probability of a trough concentration ≤1 mg/L increased with an ODD/EID regimen (odds ratio, 7.23; 95% confidence interval: 3.48-15.0, P < 0.001) and in the postguidelines group (odds ratio, 2.02; 95% confidence interval: 1.01-4.02, P = 0.045). Guideline implementation generated a sharp reduction in blood sampling. Clinical benefits of better gentamicin dosing and TDM practices were evident. Cost-effectiveness and clinical benefit of reduced blood sampling should be evaluated.

A survey of extended-interval aminoglycoside dosing practices in United States adult cystic fibrosis programs.

The Cystic Fibrosis Foundation recently deemed the use of extended-interval dosing (EID) of aminoglycosides acceptable for the treatment of cystic fibrosis (CF) pulmonary exacerbations. However, current practice across United States adult CF programs and affiliate programs is unknown. The objectives of this research are to characterize the practice trends, dosing strategies, therapeutic drug-monitoring practices, and adverse effect monitoring of the EID of aminoglycosides in the treatment of pulmonary exacerbations across United States adult CF programs. A 34-question online survey instrument was distributed on behalf of the author by the United States Cystic Fibrosis Foundation to all United States adult CF programs and affiliate programs. Of the 68 participating adult CF programs (44.4% survey response rate), 64 (94.1%) reported using EID of aminoglycosides (as once-daily or twice-daily dosing). More than 95% of programs reported frequently or always using this dosing method. Tobramycin dosed 10 mg/kg/d every 24 h, infused over 30-60 min, was the most commonly cited regimen. Monitoring of aminoglycoside serum concentrations was reported by all programs, with a tobramycin peak of 25-30 mg/L and trough of < 1 mg/L targeted most frequently. Nephrotoxicity was commonly monitored through serum creatinine measurements, while ototoxicity was monitored by audiometry in approximately one-half of programs. This study indicates that the use of EID of aminoglycosides across United States adult CF programs has increased considerably since the publication of the CF pulmonary exacerbation guidelines and now appears to be the most common method for dosing aminoglycosides in adults with CF.

PP197—Therapeutic Drug Monitoring of Vancomycin and Aminoglycosides in an Intensive Care Unit, a Retrospective Study

Critically ill patients may display altered pharmacokinetic parameters. Therapeutic drug monitoring (TDM) is essential to optimize the use of antibiotics in intensive care units. Many TDM assessments may be inappropriate as a result of improper interpretation or collection timing. We assessed the practice of TDM of vancomycin and aminoglycosides in an adult intensive care unit.

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy. Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM. The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly. For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum. Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting. Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent.

Evaluating Appropriateness of Digoxin, Carbamazepine, Valproic Acid, and Phenytoin Usage by Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) is a useful tool for the optimization of drug therapy. The aim of this retrospective study was to evaluate the appropriateness of carbamazepine, phenytoin, valproic acid, and digoxin therapy by using TDM data. We evaluated the appropriateness of drug usage in 325 patients who received carbamazepine, valproic acid, phenytoin, or digoxin in a large teaching hospital during the period from March 2010 to January 2011. The serum drug levels were measured by cloned enzyme donor immunoassay (CEDIA). A total of 325 TDM tests were performed in this period. In our TDM unit, valproic acid was the most evaluated test among the samples obtained. In 100 valproic acid-treated patients, serum levels in 58 patients (58%) were within the therapeutic range. While 11 patients (11%) had serum levels in the above-therapeutic range, 31 patients (31%) had sub-therapeutic levels of valproic acid: The results of TDM were mostly found in the therapeutic range for carbamazepine. A total of 91 request forms were collected. The overall data show that 64 patients (70.3%) had serum carbamazepine levels within the therapeutic range. In the phenytoin assays, the mean plasma concentrations generally did not reach the therapeutic range. Among the total of 49 blood samples, the highest number of sub-therapeutic levels (65.3%) were detected for phenytoin. Similarly, inappropriate levels of digoxin were established in about half of all cases. This study gives information about the inappropriate usage of digoxin and phenytoin in respect to the results of our TDM practice. Our results suggest that there is a need for interventions to improve the appropriate use of digoxin and phenytoin in patients treated with these drugs.

Therapeutic Drug Monitoring for Antidepressant Drug Treatment

The aim of antidepressant drug treatment is to produce remission without causing adverse effects during the acute phase of the illness and to prevent relapses or recurrences during continuation or maintenance therapy. To achieve these goals, drug choice and dosage must be optimized for each patient individually. Therapeutic drug monitoring (TDM), which is based on the assumption that clinical effects correlate better with blood levels than doses, can be helpful. When using tricyclic antidepressant drugs TDM enhances safety and efficacy. For newer antidepressant drugs, however, it is a matter of debate to which extend TDM can have beneficial effects. For many antidepressants there exist carefully designed studies concerning the relationship between plasma concentration and clinical effects that allow the definition of recommended therapeutic ranges of the plasma concentration. In some drugs however, concentration-effect studies are lacking so far, but target ranges resulting from clinically relevant plasma concentrations or from pharmacokinetic studies could be provided. During the last years, knowledge on therapeutic references ranges in blood towards TDM guided treatment has markedly improved for new antidepressant drugs, and many specific indications have been defined for useful TDM. Recently published guidelines describe the best practice of TDM for neuropsychiatric drugs. The aim of this review is to summarize the current status of TDM for antidepressant drugs and discuss the literature with regard to response optimization, pharmacovigilance and economic benefits and with regard to needs for further research.

Inappropriate Vancomycin Therapeutic Drug Monitoring in Hospitalized Pediatric Patients Increases Pediatric Trauma and Hospital Costs

The objective of this study was to measure the appropriateness of vancomycin monitoring in a pediatric tertiary care center and to evaluate the effectiveness of two interventions, autonomous pharmacy therapeutic drug monitoring and health care provider education, in reducing avoidable pediatric patient trauma and hospital cost. A retrospective chart review evaluating vancomycin therapeutic drug monitoring (TDM) in pediatric inpatients was performed before and after the introduction of an autonomous pharmacy TDM program and health care provider (HCP) education. Thirty-five patients were included in our study, prior to any intervention. Of these, 9% of patients had trough concentrations appropriately deferred. Of the total of 64 trough concentrations obtained, 94% were considered to be inappropriate. After the start of the autonomous pharmacy TDM program, of the 54 eligible patients (111 troughs), 9% had trough concentrations appropriately deferred, and 34% were inappropriate. In the 3-month period following the introduction of HCP education in combination with pharmacy TDM, we identified 27 eligible patients. Among those, 15% of the patients had trough concentrations appropriately deferred. Of the 43 trough concentrations obtained, only 9% were considered to be inappropriate. The combination of pharmacy TDM with HCP education decreased annualized hospital cost by 60%, from $13,080 to $5232. Inappropriate vancomycin TDM occurs commonly in our institution, resulting in unnecessary hospital cost and patient trauma. The combination of pharmacy TDM and HCP education significantly improved clinical practice; however, results were short-lived. Further interventions, such as computer based order entry, will likely be needed to reinforce and improve long-term TDM practice in pediatric patients.

Effects of clinical decision support on the TDM of gentamicin and vancomycin in newborns

BackgroundThe dosing scheme for gentamicin and therapeutic drug monitoring (TDM) of gentamicin and vancomycin in newborns were evaluated as very heterogeneous in our institution. Once daily dosing (ODD) of gentamicin...

TDM and stabilisation of paediatric patients in liver and kidney transplantation

BackgroundImmunosuppressants must be guided by therapeutic drug monitoring (TDM) to prevent rejection. Understanding and prevention of blood level variability is essential.PurposeTo evaluate TDM practice and factors associated with stabilisation.Materials and...

A survey of therapeutic drug monitoring services in Malaysia

In Malaysia, therapeutic drug monitoring (TDM) service was started in the 1980s. Since then, the number of hospitals that offer the service has increased. In this paper, we report the findings of a nationwide survey describing the practice of TDM in these hospitals. Questionnaires were mailed to 128 government hospitals. Data were collected for general characteristics of the hospitals, administrative, and laboratory activities related to TDM service. One hundred and twenty-one hospitals responded to the survey. Thirty-four hospitals (28.1%) provided the service with their own TDM laboratories, 44 hospitals (36.4%) provided the service using other hospitals’ laboratories and 43 hospitals (35.5%) did not provide the service at all. TDM services were more likely to be offered in larger hospitals with various medical specialties. Since it is managed entirely by hospital pharmacists, these pharmacists assume an important role in ensuring optimum use of the TDM service.

National Survey of Extended-Interval Aminoglycoside Dosing in Pediatric Cystic Fibrosis Pulmonary Exacerbations

The Cystic Fibrosis Foundation recently deemed the use of extended-interval dosing (EID) of aminoglycosides acceptable for the treatment of cystic fibrosis (CF) pulmonary exacerbations, but current practices across United States (US) pediatric CF accredited care centers and affiliate programs are unknown. The objectives of this research are to characterize the practice trends, dosing strategies, therapeutic drug monitoring practices, and adverse drug reaction monitoring of EID of aminoglycosides in the treatment of pulmonary exacerbations across US pediatric CF programs. A 38-question online survey was distributed on behalf of the author by the CF Foundation to all US pediatric CF accredited care centers and affiliate programs. Of the 70 participating CF programs (42.2% survey response rate), 94.3% reported using EID of aminoglycosides (as once-daily or twice-daily dosing), whereas 84.3% reported using once-daily EID in their pediatric CF population. The frequency of EID use increased with patient age. Tobramycin dosed 10 mg/kg per day every 24 hours, infused over the course of 30 minutes, in combination with an antipseudomonal beta-lactam, was the most commonly cited regimen. Monitoring of aminoglycoside serum concentrations was reported by 98.5% of programs, with a tobramycin peak of 25 to 30 mg/L and trough of less than 1 mg/L targeted most frequently. Nephrotoxicity was commonly monitored through serum creatinine measurements, whereas ototoxicity was monitored by audiometry in approximately one-half of programs. This study indicates that the use of EID of aminoglycosides across US pediatric CF accredited care centers and affiliate programs is common, particularly among adolescents, with tobramycin being the preferred agent.

Determination of daptomycin in human plasma by liquid chromatography-tandem mass spectrometry. Clinical application

Daptomycin is a recently developed cyclic lipopeptide antibiotic active against most Gram-positive pathogens including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. To optimize treatment efficacy and safety, especially in patients undergoing multiple drug regimens and/or co-morbidities, a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of daptomycin in plasma. A C18 column was used for separation, with a mobile phase initially consisting of 0.1% formic acid, water, and acetonitrile (ACN) in a linear gradient from 20% to 70%. After protein precipitation with ACN, the clear upper layer was diluted in water:ACN (50:50, v/v) before injection. Detection was performed using an electrospray ionization technique. MS/MS transitions, monitored in the positive ion mode were m/z 811.1 → m/z 313.1 for daptomycin, and m/z 609.4 → m/z 194.9 for reserpine, used as internal standard. Elution of daptomycin and reserpine occurred at 4.5 and 3.9 min, respectively. The method was validated over a range of concentrations from 1 mg/L to 120 mg/L. The assay met recommended acceptance criteria: coefficients of variation were <6.3% and <7.4%, and accuracies were between -5.9% and +11.2% and between -3.5% and +3.7%, for intra- and inter-day validations, respectively. This method appears well-adapted to routine hospital practice for therapeutic drug monitoring of daptomycin considering its time of analysis, range of concentrations measured, precision and accuracy.

French summaries of product characteristics: content in relation to therapeutic monitoring of psychotropic drugs

The prescription information (summary of product characteristics, SPC) is compiled by the pharmaceutical industry as required by the national regulatory authorities. They vary in their content about the properties of drugs and about the usefulness of therapeutic drug monitoring (TDM) in the blood of patients. Based on a previous study carried out in Germany, the degree of agreement of French SPC for 59 psychotropic drugs with the existing medico-scientific evidence in the area of TDM was examined using a recently developed instrument. A summary score of SPC content (SPCC) related to TDM (SPCC(TDM)) has been calculated and compared with the level of recommendation of TDM of the AGNP-TDM expert group consensus guidelines for TDM in psychiatry [AGNP: Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (Association for neuropsychopharmacology and pharmacopsychiatry)]. Among the antidepressants, antipsychotics, tranquillizers/hypnotic agents and mood stabilizers, the highest SPCC(TDM) scores in the French SPC were reached for imipramine (16), haloperidol (6), clonazepam (8) and lithium (23), respectively. Results were similar to those obtained from the analysis of German SPC, and considerable disagreement was found between the information on TDM in SPC and existing medico-scientific evidence, albeit less in the case of mood stabilizers. Taking into account the recommendations of the AGNP-TDM expert group guidelines, there is a deficit in the French SPC concerning TDM-relevant information. An amelioration of this situation could help to improve the clinical practice of TDM of psychotropic drugs, as the SPC is a widely used tool.

PROMOTION OF AN APPLIED PHARMACOKINETIC SOFTWARE, NAMED PHARMONITOR, DEVELOPED TO OPTIMIZE INDIVIDUAL DOSAGE REGIMEN THROUGH A NATIONAL QUALITY CONTROL PROGRAM

To improve the practice of therapeutic drug monitoring, the Belgian Health Authorities have decided to support the development of an upgraded version of a pharmacokinetic program, so-called PharMonitor 1.0.0. Based on the Sawchuk-Zaske method, this software is a valuable and user-friendly tool for individually adjusting dosage regimens of aminoglycosides. It allows maximal speed, flexibility, reliability and optimal traceability. Moreover, the software is easily customized according to the user’s selection (language, concentration units, drug target ranges, creatinine clearance, …). Reports can be generated in PDF format after appropriate validation. The software can be connected to most laboratory information systems. Additional applications should be developed on PharMonitor 1.0.0. (other classes of drugs, Bayesian approach, …). Once freely distributed to all Belgian laboratories, this software is expected to reduce the variability observed through external quality assessment schemes (EQAS), in the interpretation of drug concentrations.