scholarly journals The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants

2005 ◽  
Vol 7 (3) ◽  
pp. 231-247 ◽  
Keyword(s):  
Clinical Laboratory ◽  
Psychiatric Patients ◽  
Plasma Concentrations ◽  
Clinical Effectiveness ◽  
Drug Analysis ◽  
Therapeutic Monitoring ◽  
Patient Treatment ◽  
Therapeutic Drug ◽  
Pharmacokinetic Studies ◽  
Consensus Guidelines

Therapeutic drug monitoring (TDM) of psychotropic drugs such as antidepressants has been widely introduced for optimization of pharmacotherapy in psychiatric patients. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has worked out consensus guidelines with the aim of providing psychiatrists and TDM laboratories with a tool to optimize the use of TDM. Five research-based levels of recommendation were defined with regard to routine monitoring of drug plasma concentrations: (i) strongly recommended; (ii) recommended; (iii) useful; (iv) probably useful; and (v) not recommended. In addition, a list of indications that justify the use of TDM is presented, eg, control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning drug metabolism, and children, adolescents, and elderly patients. For some drugs, studies on therapeutic ranges are lacking, but target ranges for clinically relevant plasma concentrations are presented for most drugs, based on pharmacokinetic studies reported in the literature. For many antidepressants, a thorough analysis of the literature on studies dealing with the plasma concentration-clinical effectiveness relationship allowed inclusion of therapeutic ranges of plasma concentrations. In addition, recommendations are made with regard to the combination of pharmacogenetic (phenotyping or genotyping) tests with TDM. Finally, practical instructions are given for the laboratory practitioners and the treating physicians how to use TDM: preparation of TDM, drug analysis, reporting and interpretation of results, and adequate use of information for patient treatment TDM is a complex process that needs optimal interdisciplinary coordination of a procedure implicating patients, treating physicians, clinical pharmacologists, and clinical laboratory specialists. These consensus guidelines should be helpful for optimizing TDM of antidepressants.

Pharmacokinetics of culture-directed antibiotics for the treatment of peritonitis in automated peritoneal dialysis: A systematic narrative review

2021 ◽  
Vol 41 (3) ◽  
pp. 261-272
Author(s):  
Chau Wei Ling ◽  
Kamal Sud ◽  
Connie Van ◽  
Syed Tabish Razi Zaidi ◽  
Rahul P. Patel ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Case Reports ◽  
Plasma Concentrations ◽  
Case Series ◽  
Therapeutic Drug ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Data ◽  
Automated Peritoneal Dialysis ◽  
Final Study ◽  
Drug Plasma

The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.

Plasma vs whole blood for therapeutic drug monitoring of patients receiving FK 506 for immunosuppression

1994 ◽  
Vol 40 (12) ◽  
pp. 2247-2253 ◽  
Author(s):  
M Winkler ◽  
B Ringe ◽  
J Baumann ◽  
M Loss ◽  
K Wonigeit ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Enzyme Immunoassay ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Plasma Concentrations ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Fk 506 ◽  
Blood Samples ◽  
The Matrix

Abstract By retrospective analysis of 13,000 blood samples obtained from 248 patients receiving FK 506 therapy, we compared the suitability of plasma with that of whole blood as the matrix for therapeutic drug monitoring of FK 506. The plasma concentrations did not correlate with the concentrations in whole blood (r = 0.56). In contrast to plasma samples (analyzed by enzyme immunoassay), FK 506 was detectable in all whole-blood samples (analyzed by enzyme immunoassay/microparticle enzyme immunoassay). The inter- and intraindividual variations of FK 506 measurements were greater in plasma than in whole blood. Moreover, plasma concentrations correlated only poorly with clinical events. There was a tendency to greater plasma concentrations being measured during episodes of toxicity, but no clear difference was evident between stable course and rejection. In whole-blood specimens, a correlation between reduced or increased FK 506 concentrations and rejection or toxicity, respectively, was observed. The discriminatory power of whole-blood values was greater for the differentiation between toxicity and stable course than between rejection and stable course. We therefore recommend whole blood rather than plasma as the matrix for therapeutic monitoring of FK 506 concentrations.

scholarly journals Pharmacokinetics of Posaconazole Suspension in Lung Transplant Patients with and without Cystic Fibrosis

2016 ◽  
Vol 60 (6) ◽  
pp. 3558-3562 ◽  
Author(s):  
Hongfei Zhang ◽  
M. Hong Nguyen ◽  
Cornelius J. Clancy ◽  
Rujuta Joshi ◽  
Wenchen Zhao ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Transplant ◽  
Fungal Infections ◽  
Plasma Concentrations ◽  
Treatment Strategies ◽  
Area Under The Curve ◽  
Therapeutic Drug ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Data ◽  
Average Dose

Invasive fungal infections (IFIs) are common among lung transplant recipients (LTRs). Posaconazole is an important antifungal agent for both prophylaxis and treatment of IFIs; however, detailed pharmacokinetic data are limited among LTRs, particularly those with cystic fibrosis (CF). Our objective was to conduct a pharmacokinetic study of posaconazole oral suspension among LTRs, with particular attention to patients with CF. We enrolled 20 LTRs, 7 with CF and 13 with other underlying lung diseases. Average daily doses in CF and non-CF patients were 829 and 862 mg, respectively. After ≥5 days of treatment, only 4 patients had average plasma concentrations of >0.7 μg/ml. Average steady-state plasma concentrations were 61% lower in CF patients (0.233 μg/ml) than in non-CF LTRs (0.594 μg/ml;P= 0.03). The average dose-normalized plasma area-under-the-curve (AUC) values were also lower in CF (0.007 h·μg/ml) than in non-CF LTRs (0.02 h·μg/ml;P= 0.02). The weight-normalized apparent oral clearance values were 2.51 and 0.74 liters/h/kg among CF and non-CF LTRs, respectively (P= 0.005). Despite significant interpatient variability, plasma trough concentrations were strongly correlated with posaconazole AUC across all LTRs (r2= 0.95,P< 0.0001). Taken together, our study highlights a critical need to incorporate new formulations of posaconazole into prophylaxis and treatment strategies for LTRs, particularly those with CF. Future pharmacokinetic studies of both tablet and intravenous formulations must consider LTR-specific factors and incorporate a therapeutic drug monitoring plan in this patient population.

Effect of Heat Treatment of Potentially Infected Blood Samples on Therapeutic Drug Monitoring of Selected Drugs

1993 ◽  
Vol 27 (7-8) ◽  
pp. 887-888 ◽  
Author(s):  
David M. Burger ◽  
Elisabeth A. van Dijk ◽  
Roel van Gijn ◽  
Jos H. Beijnen
Keyword(s):  
Heat Treatment ◽  
Valproic Acid ◽  
Whole Blood ◽  
Drug Analysis ◽  
Therapeutic Monitoring ◽  
Rank Test ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Signed Rank ◽  
Signed Rank Test

OBJECTIVE: To investigate the effect of heat treatment on the outcome of drug analysis in whole blood and serum for eight drugs routinely assayed for therapeutic monitoring. DESIGN: All blood and serum samples (n=373) received at the pharmacy laboratory for therapeutic monitoring of carbamazepine, digoxin, gentamicin, kanamycin, phenobarbital, phenytoin, theophylline, and valproic acid were heated at 60°C for 30 minutes. Serum was subsequently assayed by fluorescence polarization immunoassay (TDx). SETTING: The study was conducted at the analytical laboratory of the pharmacy, using standard laboratory procedures. MAIN OUTCOME MEASURES: Analyses of heated samples were compared with analyses of untreated samples using a paired Wilcoxon signed-rank test. RESULTS: Serum concentrations of phenytoin from treated whole blood, and of gentamicin in treated serum, were significantly lower than in untreated samples. These differences, however, were small, clinically irrelevant, and lie within assay variation intervals. Heat treatment did not influence the outcome of analyses for carbamazepine, digoxin, kanamycin, phenobarbital, theophylline, and valproic acid. CONCLUSIONS: Heat treatment of whole blood and serum samples of the investigated drugs does not influence the outcome of drug analysis, although drug instability cannot be fully excluded. Heat treatment can protect laboratory technicians from HIV infection without influencing therapeutic monitoring of these drugs.

The AGNP-TDM Expert Group Consensus Guidelines: Therapeutic Drug Monitoring in Psychiatry

2005 ◽  
Vol 38 (01) ◽  
Author(s):  
I Gaertner ◽  
P Baumann ◽  
C Hiemke ◽  
S Ulrich ◽  
G Eckermann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Expert Group ◽  
Group Consensus ◽  
Consensus Guidelines

scholarly journals Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low

2021 ◽  
Author(s):  
E. Heinonen ◽  
M. Blennow ◽  
M. Blomdahl-Wetterholm ◽  
M. Hovstadius ◽  
J. Nasiell ◽  
...  
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Plasma Concentrations ◽  
Relative Difference ◽  
Interindividual Variation ◽  
Therapeutic Drug ◽  
Cytochrome P450 Enzyme ◽  
Second Trimester ◽  
P450 Enzyme ◽  
Placental Passage

Abstract Purpose Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. Method Pregnant women with moderate untreated depression were recruited in 2016–2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. Results Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers’, measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. Conclusion Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. Trial registration The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

scholarly journals 182. Missed Opportunities to Discontinue Unnecessary Vancomycin During Pharmacist Therapeutic Monitoring

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S98-S98
Author(s):  
Corey J Medler ◽  
Mary Whitney ◽  
Juan Galvan-Cruz ◽  
Ron Kendall ◽  
Rachel Kenney ◽  
...  
Keyword(s):  
Length Of Stay ◽  
Adverse Drug Events ◽  
Academic Medical Center ◽  
Total Duration ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Therapeutic Monitoring ◽  
Resistant Bacteria ◽  
Therapeutic Drug ◽  
Missed Opportunities

Abstract Background Unnecessary and prolonged IV vancomycin exposure increases risk of adverse drug events, notably nephrotoxicity, which may result in prolonged hospital length of stay. The purpose of this study is to identify areas of improvement in antimicrobial stewardship for vancomycin appropriateness by clinical pharmacists at the time of therapeutic drug monitoring (TDM). Methods Retrospective, observational cohort study at an academic medical center and a community hospital. Inclusion: patient over 18 years, received at least three days of IV vancomycin where the clinical pharmacy TDM service assessed for appropriate continuation for hospital admission between June 19, 2019 and June 30, 2019. Exclusion: vancomycin prophylaxis or administered by routes other than IV. Primary outcome was to determine the frequency and clinical components of inappropriate vancomycin continuation at the time of TDM. Inappropriate vancomycin continuation was defined as cultures positive for methicillin-susceptible Staphylococcus aureus (MRSA), vancomycin-resistant bacteria, and non-purulent skin and soft tissue infection (SSTI) in the absence of vasopressors. Data was reported using descriptive statistics and measures of central tendency. Results 167 patients met inclusion criteria with 38.3% from the ICU. SSTIs were most common indication 39 (23.4%) cases, followed by pneumonia and blood with 34 (20.4%) cases each. At time of vancomycin TDM assessment, vancomycin continuation was appropriate 59.3% of the time. Mean of 4.22 ± 2.69 days of appropriate vancomycin use, 2.18 ± 2.47 days of inappropriate use, and total duration 5.42 ± 2.94. 16.4% patients developed an AKI. Majority of missed opportunities were attributed to non-purulent SSTI (28.2%) and missed MRSA nares swabs in 21% pneumonia cases (table 1). Conclusion Vancomycin is used extensively for empiric treatment of presumed infections. Appropriate de-escalation of vancomycin therapy is important to decrease the incidence of adverse effects, decreasing hospital length of stay, and reduce development of resistance. According to the mean duration of inappropriate therapy, there are opportunities for pharmacy and antibiotic stewardship involvement at the time of TDM to optimize patient care (table 1). Missed opportunities for vancomycin de-escalation Disclosures All Authors: No reported disclosures

scholarly journals Clinical Implications of Polymicrobial Synergism Effects on Antimicrobial Susceptibility

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 144
Author(s):  
William Little ◽  
Caroline Black ◽  
Allie Clinton Smith
Keyword(s):  
Antimicrobial Susceptibility ◽  
Chronic Wounds ◽  
Clinical Laboratory ◽  
Patient Treatment ◽  
Clinical Implications ◽  
Clinical Environment ◽  
Tolerance Mechanisms ◽  
Sequencing Technologies ◽  
Generation Sequencing ◽  
Polymicrobial Infections

With the development of next generation sequencing technologies in recent years, it has been demonstrated that many human infectious processes, including chronic wounds, cystic fibrosis, and otitis media, are associated with a polymicrobial burden. Research has also demonstrated that polymicrobial infections tend to be associated with treatment failure and worse patient prognoses. Despite the importance of the polymicrobial nature of many infection states, the current clinical standard for determining antimicrobial susceptibility in the clinical laboratory is exclusively performed on unimicrobial suspensions. There is a growing body of research demonstrating that microorganisms in a polymicrobial environment can synergize their activities associated with a variety of outcomes, including changes to their antimicrobial susceptibility through both resistance and tolerance mechanisms. This review highlights the current body of work describing polymicrobial synergism, both inter- and intra-kingdom, impacting antimicrobial susceptibility. Given the importance of polymicrobial synergism in the clinical environment, a new system of determining antimicrobial susceptibility from polymicrobial infections may significantly impact patient treatment and outcomes.

scholarly journals Impact on Antibiotic Resistance, Therapeutic Success, and Control of Side Effects in Therapeutic Drug Monitoring (TDM) of Daptomycin: A Scoping Review

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 263
Author(s):  
Carolina Osorio ◽  
Laura Garzón ◽  
Diego Jaimes ◽  
Edwin Silva ◽  
Rosa-Helena Bustos
Keyword(s):  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Bacterial Resistance ◽  
Plasma Concentrations ◽  
Resistant Bacteria ◽  
Therapeutic Drug ◽  
Therapeutic Success ◽  
Favorable Clinical Outcome ◽  
And Control

Antimicrobial resistance (AR) is a problem that threatens the search for adequate safe and effective antibiotic therapy against multi-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE) and Clostridium difficile, among others. Daptomycin is the treatment of choice for some infections caused by Gram-positive bacteria, indicated most of the time in patients with special clinical conditions where its high pharmacokinetic variability (PK) does not allow adequate plasma concentrations to be reached. The objective of this review is to describe the data available about the type of therapeutic drug monitoring (TDM) method used and described so far in hospitalized patients with daptomycin and to describe its impact on therapeutic success, suppression of bacterial resistance, and control of side effects. The need to create worldwide strategies for the appropriate use of antibiotics is clear, and one of these is the performance of therapeutic drug monitoring (TDM). TDM helps to achieve a dose adjustment and obtain a favorable clinical outcome for patients by measuring plasma concentrations of an administered drug, making a rational interpretation guided by a predefined concentration range, and, thus, adjusting dosages individually.

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