The relationship between ritonavir plasma levels and side-effects: implications for therapeutic drug monitoring

AIDS ◽  
1999 ◽  
Vol 13 (15) ◽  
pp. 2083-2089 ◽  
Author(s):  
Giorgio Gatti ◽  
Antonio Di Biagio ◽  
Rosetta Casazza ◽  
Cleta De Pascalis ◽  
Matteo Bassetti ◽  
...  
Keyword(s):  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Plasma Levels ◽  
Therapeutic Drug ◽  
The Relationship

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.

scholarly journals Thiopurines’ Metabolites and Drug Toxicity: A Meta-Analysis

2020 ◽  
Vol 9 (7) ◽  
pp. 2216
Author(s):  
Paula Sousa ◽  
Maria Manuela Estevinho ◽  
Cláudia Camila Dias ◽  
Paula Ministro ◽  
Uri Kopylov ◽  
...  
Keyword(s):  
Systematic Review ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Alanine Aminotransferase ◽  
Odds Ratio ◽  
Drug Toxicity ◽  
Meta Analysis ◽  
Therapeutic Drug ◽  
Gastrointestinal Intolerance ◽  
The Relationship

Many questions remain unanswered regarding therapeutic drug monitoring (TDM) utility with thiopurines. This study aims to establish a relationship between thiopurines’ metabolites and drug toxicity. We performed a systematic review with inclusion of studies evaluating the relationship between thiopurines’ metabolites and drug toxicity. Meta-analysis of mean difference (MD), correlations and odds ratio (OR) was performed. We identified 21,240 records, 72 of which were eligible for meta-analysis. Levels of 6-thioguanine nucleotides (6-TGN) were higher in patients with leukopenia (MD 127.06 pmol/8 × 108 RBC) and gastrointestinal intolerance (MD 201.46 pmol/8 × 108 RBC), and lower in patients with hepatotoxicity (MD −40.6 pmol × 108 RBC). We established a significant correlation between 6-TGN and leukocytes (r = −0.21), neutrophils (r = −0.24) and alanine aminotransferase levels (r = −0.24). OR for leukopenia in patients with elevated 6-TGN was 4.63 (95% CI 2.24; 9.57). An optimal cut-off of 135 pmol/8 × 108 RBC for leukopenia was calculated (sensitivity 75.4%; specificity 46.4%). 6-methylmercaptopurine ribonucleotides (6-MMPR) were significantly associated with hepatotoxicity (MD 3241.2 pmol/8 × 108 RBC; OR 4.28; 95% CI 3.20; 5.71). Levels of 6-MMPR measured in the first 8 weeks of treatment were associated with leukopenia. We conclude that TDM could be used to prevent thiopurines’ toxicity. As optimal metabolites level may vary according to indication, physicians may adapt posology to decrease toxicity without compromising efficacy.

Ictal aggression in severely mentally handicapped people

1993 ◽  
Vol 10 (1) ◽  
pp. 12-15 ◽  
Author(s):  
Mary Creaby ◽  
Mary Warner ◽  
Nahla Jamil ◽  
Sudad Jawad
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Seizure Frequency ◽  
Drug Monitoring ◽  
Aggressive Behaviour ◽  
Therapeutic Drug ◽  
Neuroleptic Drugs ◽  
Partial Seizures ◽  
Mentally Handicapped ◽  
Handicapped People ◽  
The Relationship

AbstractObjective: To study the relationship between epilepsy and aggression in a population of severely mentally handicapped people. Methods: Comparing epilepsy and aggression variables in people with epilepsy without aggression, people with aggression without epilepsy, and people with both. The epilepsy variables were: seizure frequency, classification, anticonvulsant drugs, therapeutic drug monitoring, and neuroleptic drugs. Aggression variables were: frequency, direction, type, and neuroleptic drugs. Results: Prevalence of aggressive behaviour was similar in people with and without epilepsy (36%). Partial seizures were less prevalent in people with epilepsy and aggression. People with epilepsy were more likely to manifest unprovoked aggression directed against property. Conclusion: Some episodes of aggressive behaviour in people with epilepsy may be ictal in origin.

scholarly journals Use of Therapeutic Drug Monitoring to Characterize Cefepime-Induced Neurotoxicity

2020 ◽  
Author(s):  
Veena Venugopalan ◽  
Cara Nys ◽  
Natalie Hurst ◽  
Yiqing Chen ◽  
Maria Bruzzone ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Hospitalized Patients ◽  
Therapeutic Drug ◽  
Eeg Abnormalities ◽  
Increased Risk ◽  
Trough Concentrations ◽  
The Relationship

AbstractBackgroundThe incidence of cefepime-induced neurotoxicity (CIN) in hospitalized patients is highly variable. Although greater cefepime exposures incite neurotoxicity, data evaluating trough thresholds associated with CIN remains limited. The objectives of this study were to evaluate the incidence of CIN, assess the relationship between cefepime trough concentrations and CIN, investigate clinical factors associated with CIN, and describe electroencephalogram (EEG) abnormalities in CIN.MethodsThis was a retrospective study of adult patients who had received ≥ 5 days of cefepime with ≥ 1 trough concentration > 25 mg/L. Potential CIN cases were identified utilizing neurological symptoms, neurologist assessments, EEG findings and improvement of neurotoxicity after cefepime discontinuation.ResultsOne-hundred and forty-two patients were included. The incidence of CIN was 13% (18/142). The mean cefepime trough concentration in CIN patients was significantly greater than the non-neurotoxicity group (74.2 mg/L ± 41.1 vs. 46.6 mg/L ± 23, p=0.015). Lower renal function (creatinine clearance < 30 ml/min), greater time to therapeutic drug monitoring (TDM) (≥72 hours), and each 1 mg/mL rise in cefepime trough were independently associated with increased risk of CIN. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CIN.ConclusionCefepime should be used cautiously in hospitalized patients due to the risk of neurotoxicity. Patients with greater renal function and those who had early cefepime TDM (≤ 72 hours) had lower risk of CIN.

scholarly journals The relationship between tacrolimus concentration-dose ratio and genetic polymorphism in patients subjected to renal transplantation

2018 ◽  
Vol 75 (2) ◽  
pp. 147-153 ◽  
Author(s):  
Nemanja Rancic ◽  
Neven Vavic ◽  
Bojana Cikota-Aleksic ◽  
Zvonko Magic ◽  
Momir Mikov ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Tacrolimus Concentration ◽  
Therapeutic Drug ◽  
Monitoring Strategy ◽  
Dose Ratio ◽  
P Glycoprotein ◽  
Case Series Study ◽  
The Relationship

Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal transplantation. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio, suggested to be used as a therapeutic drug monitoring strategy and the polymorphisms of genes encoding the most important enzymes, such as CYP3A5 and CYP3A4, as well as the transporter P-glycoprotein, for its metabolism and elimination. Methods. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real- Time PCR System by assessing allelic discrimination based on TaqMan? methodology. Results. Patients (n = 13) who were treated with less than 2 mg of tacrolimus/day (0.024 ? 0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/mL/mg/kg. In this group, 84.62% patients had CYP3?5 *3*3 allele. All of these patients had CYP3?4 *1*1/*1*1B allele. Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant, while 69.23% of our patients had CC and CT gene variants. Conclusion. Tacrolimus concentration-dose ratio greater than 150 ng/mL/mg/kg is cut-off value in patients subjected to renal transplantation which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein.

scholarly journals TRICYCLIC ANTIDEPRESSANTS;

2012 ◽  
Vol 19 (02) ◽  
pp. 197-201
Author(s):  
Shah KHALID ◽  
MOWADAT HUSSAIN RANA ◽  
NAJAM AKHTAR
Keyword(s):  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Study Design ◽  
Drug Monitoring ◽  
Lower Incidence ◽  
Tricyclic Antidepressant ◽  
Military Hospital ◽  
Therapeutic Drug ◽  
Control Group ◽  
Treatment Of Depression

Introduction: Despite advancements in the treatment of depression and availability of newer compounds, TCAs likeamitriptyline remain to be the cornerstone of antidepressive therapy for more than three decades, however significantly more patients receivinga tricyclic withdraw from treatment mainly because of side effects. Higher response, lower incidence of side effects and improved compliancecan be enhanced by the optimal use of Therapeutic Drug Monitoring (TDM). No research data is currently available on the therapeutic drugmonitoring of TCAs in Pakistan. Objectives: To compare the relative efficacy of Tricyclic antidepressant in the treatment of depression, with andwithout Therapeutic Drug Monitoring Main Outcome Measures: Changes in HAMD scores in patients on TCAs. Study Design: A Quasiexperimental study design was used. Setting: The study was conducted at Department of Psychiatry, Military Hospital Rawalpindi. Subjects:34 patients completed the study in the monitored group (with TDM) and 33 in control group (without TDM). Methods: Serum TCA levels andHAMD scores at baseline and subsequently at sixth, eighth and tenth week of treatment were collected. In all the subjects, all the blood sampleswere drawn as a fasting sample in early morning. Results: The mean age of the monitored group was 31.97 years (SD=10.432) while that of thecontrol group was 33.52 years (SD=9.385). in the monitored group 20 (58.82 %) of the patients were males while 14 (41.17%) were females, inthe control group 22 (66.66%) were males and 11(33.33%) were female patients. A significant reduction in HAMD scores was noted at 8 weeksof treatment. The groups did not differ in terms of efficacy of TCAs, however the monitored group had fewer dropouts than the control group.Conclusions: Lower incidence of side effects and improved compliance can be enhanced by the optimal use of Therapeutic Drug Monitoring(TDM) of TCAs.

Therapeutic Drug Monitoring of Tipranavir: About 2 Cases of Adverse Side Effects

Drug Safety ◽  
2007 ◽  
Vol 30 (10) ◽  
pp. 919-990
Author(s):  
A S Lemaire-Hurtel ◽  
L Masson ◽  
L Hary ◽  
H Masson ◽  
M Andrejak
Keyword(s):  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Adverse Side Effects

scholarly journals Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks

2020 ◽  
Vol 8 (3) ◽  
pp. 415 ◽  
Author(s):  
Stefan Felix Ehrentraut ◽  
Stefan Muenster ◽  
Stefan Kreyer ◽  
Nils Ulrich Theuerkauf ◽  
Christian Bode ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Plasma Levels ◽  
Therapeutic Drug ◽  
The Right ◽  
The Impact ◽  
Current Guidelines

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.

scholarly journals Therapeutic drug monitoring in Davydovsky Hospital: using HPLC–MS/MS method in practical healthcare

2020 ◽  
Vol 4 (35) ◽  
pp. 47-52
Author(s):  
T. A. Rodina ◽  
E. S. Melnikov
Keyword(s):  
Mass Spectrometry ◽  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Dosage ◽  
Individual Therapy ◽  
Therapeutic Window ◽  
Therapeutic Drug ◽  
Tandem Mass ◽  
Anticoagulant Drugs

There was shown that therapeutic drug monitoring by liquid tandem mass spectrometry is essential not only for the drugs with a narrow therapeutic window but also for “simple” medicines like anti‑hypertension and anticoagulant drugs. The examples of choosing an individual therapy and adjusting the drug dosage to eliminate side effects were given. The cases of solving non‑standard situations that arise during bioanalytical studies were considered.

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