Therapeutic Drug Monitoring of Cyclosporine Using Single Sampling Strategy

2020 ◽  
pp. 55-63
Keyword(s):  
Steady State ◽  
Therapeutic Drug Monitoring ◽  
Clinical Outcome ◽  
Drug Exposure ◽  
Sampling Strategy ◽  
Review Article ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Total Drug ◽  
Time Points

Cyclosporine is mainly used as Immunosuppressant after different kinds of transplantation including bone marrow, lungs, kidneys, liver, heart, and other types of organ transplantations. Immunosuppressants diminish organ rejection and elongate the survival of the transplanted organs. Due to the narrow therapeutic ranges and significantly high interindividual and intraindividual variability in blood levels of cyclosporine, there is essential and vital need of therapeutic drug monitoring (TDM) of this drug in order to maintain the patient within the required therapeutic concentrations, which consequently lead to optimizing the clinical outcome and decrease the hazard of toxicity or rejection following organ transplantations. The current review article was aimed to present data for using a single or possibly two blood sampling strategy to be used for TDM of cyclosporine in order to assess the optimal blood levels of cyclosporine used in organ transplant recipients. The results showed that steady state blood concentration of cyclosporine obtained after 2 hours (C2) and possibly after 3 hours (C3) of drug administration are the best sampling time points which reflect total drug exposure (area under blood concentration versus time curve=AUC) and consequently reflecting the effect and the adverse effect(s) of cyclosporine. On the other hand, blood samples obtained at other time points particularly steady state trough concentration obtained before the next dose (C0) demonstrated poor correlation with total drug exposure and consequently the clinical outcome of the drug. Moreover, this study also demonstrated that for organs transplantations TDM of cyclosporine and assessing the clinical conditions of the patients should be routinely performed in order to adjust the dose to get optimal effect and to diminish the adverse effects of the drug. This review article focused on the findings which indicated that monitoring steady-state blood levels of cyclosporine after 2 hours (C2) and likely after 3 hours (C3) of drug intake may be used as ideal surrogate index in TDM of cyclosporine and for predicting the clinical outcome of the drug in all and different types of organs transplantations.

scholarly journals Case Report of Increased Exposure to Antiretrovirals following Sleeve Gastrectomy

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Sarah Israel ◽  
Hila Elinav ◽  
Ram Elazary ◽  
Daniel Porat ◽  
Roni Gibori ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Sleeve Gastrectomy ◽  
Case Report ◽  
Therapeutic Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Morbidly Obese ◽  
Limited Data ◽  
Time Points ◽  
Antiretroviral Drug

ABSTRACT Bariatric surgery is increasingly performed in morbidly obese HIV patients. Limited data exist regarding antiretroviral drug exposure after bariatric surgery. We report a case of a morbidly obese HIV patient who underwent sleeve gastrectomy. Abacavir, lamivudine, and dolutegravir therapeutic drug monitoring was performed at several time points pre- and postsurgery. Significantly increased levels were measured, particularly for abacavir, whose levels increased ∼12-fold. Several mechanistic explanations for these findings are discussed.

Evidence for Therapeutic Drug Monitoring of Targeted Anticancer Therapies

2012 ◽  
Vol 30 (32) ◽  
pp. 4017-4025 ◽  
Author(s):  
Bo Gao ◽  
Shang Yeap ◽  
Arthur Clements ◽  
Bavanthi Balakrishnar ◽  
Mark Wong ◽  
...  
Keyword(s):  
Steady State ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Clinical Care ◽  
Systemic Exposure ◽  
Current Evidence ◽  
Therapeutic Drug ◽  
Routine Practice ◽  
Intravenous Injections

Therapeutic drug monitoring (TDM) provides valuable guidance for dose adjustment of antibiotics, immunosuppressives, antiepileptics, and other drugs, but its use for traditional anticancer therapies has been limited. Perhaps the most important obstacle is the impractical requirement of multiple blood samples to adequately define systemic exposure of drugs that have a short elimination half-life and are given by intermittent intravenous injections. However, the newer targeted anticancer therapies have different pharmacokinetic (PK) and dosing characteristics compared with traditional cytotoxic drugs, making it possible to estimate the steady-state drug exposure with a single trough-level measurement. Recent evidence indicates that certain PK parameters, including trough levels, are correlated with clinical outcomes for many of these agents, including imatinib, sunitinib, rituximab, and cetuximab. Although the current evidence is insufficient to mandate TDM in routine practice, a concerted investigation should be encouraged to determine whether the steady-state trough measurements of targeted agents will have a practical place in the clinical care of patients with cancer.

scholarly journals Review article: a clinician's guide for therapeutic drug monitoring of infliximab in inflammatory bowel disease

2013 ◽  
Vol 38 (5) ◽  
pp. 447-459 ◽  
Author(s):  
R. Khanna ◽  
B. D. Sattin ◽  
W. Afif ◽  
E. I. Benchimol ◽  
E.-J. Bernard ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Review Article ◽  
Therapeutic Drug ◽  
Inflammatory Bowel

scholarly journals P346 Single-centre experience of ustekinumab: Therapeutic drug monitoring in Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S331-S333
Author(s):  
C Liefferinckx ◽  
M Fassin ◽  
D Thomas ◽  
C Minsart ◽  
A Cremer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Median Time ◽  
Real World ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Loss Of Response

Abstract Background Therapeutic drug monitoring (TDM) is a diagnostic tool in the monitoring of anti-TNF therapies. Yet, the benefit for TDM of new biologics such as ustekinumab (USK) is still controversial in real-world experiences. Methods This monocentric retrospective study aims to correlate USK trough levels (TLs) with clinical and endoscopic data. All patients have given written consent to the Biobank (B2011/005). Endoscopic disease was defined as quiescent in absence of endoscopic lesions, mild disease in presence of few superficial ulcerations, moderate in presence of several ulcers and severe in presence of numerous deep ulcers and/or inflammatory stenosis. 313 serum USK samples from 67 Crohn’s disease patients were used to measure USK TL (USK ELISA, apDia) while 88 samples (at week 16, and before and after optimisation) were used to measure anti-drug antibody (ADA), using a drug-tolerant affinity capture elution anti-ustekinumab assay Results Demographic and baseline data of our population are presented in Table 1. The median follow-up was 73 weeks (IQR 39–92). An optimisation due to loss of response was required in 44.8% of patients (n = 30) after a median time of 38 weeks (IQR 24–55). To evaluate the drug efficacy, an endoscopy was performed in 61% of cases at a median time of 35 weeks (IQR 27–47). TLs were 5.2 µg/ml (IQR 2.1–8.8), 1.7 µg/ml (IQR 0.3–4.3) and 2.6 µg/ml (IQR 0.6–4.1) at week 8, 16 and 24, respectively. TLs at week 8 were correlated to the induction IV dose administrated (r = 0.3, p = 0.03). At week 16, low TLs were associated with higher endoscopic activity in the follow-up (p = 0.02), although this was not the case at week 8 (p = 0.5) (Figure 1). Patients not requiring an optimisation had higher TLs in maintenance than patients requiring optimisation (2.45 µg/ml (IQR 1.3–4.4) vs. 1.15 µg/ml (IQR 0.1–2.24), p = 0.008). Obviously, optimisation significantly increased TLs (1.15 µg/ml (IQR 0.1–2.24) vs. 6.6 µg/ml (IQR 2.3–11.3), p < 0.001). ADA were undetectable in all the measured samples in maintenance. Conclusion This real-world experience confirms a drug exposure-endoscopic response relationship. Week 16 seems to be an appropriate time point to monitor drug exposure. Earlier USK TLs, at week 8, appear less valuable to be monitored due to the influence of initial IV dose. The absence of immunogenicity suggests that it is not a key driver in the loss of response.

scholarly journals Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study

2020 ◽  
Vol 10 (2) ◽  
pp. 47
Author(s):  
Giovanni Pallio ◽  
Natasha Irrera ◽  
Alessandra Bitto ◽  
Federica Mannino ◽  
Letteria Minutoli ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Therapeutic Range ◽  
Independent Predictor ◽  
National Health System ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Wild Type ◽  
Tacrolimus Pharmacokinetics

Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observation in 75 transplanted patients and to investigate if tacrolimus blood levels correlate with presence of genetic polymorphisms, thus modifying tacrolimus pharmacokinetics. CYP3A5*1 (G6986A), CYP3A4*1B (A392G), CYP3A4*22, ABCB1 (C3435T; C1236T; G2677A/T), SLCO1B1 (T521C), polymorphisms were analyzed. Based on the effect of their genotypes, patients were stratified into 5 groups: (1) reduced tacrolimus metabolism (RM), (2) increased metabolism (IM), (3) transporters polymorphisms (TM), (4) metabolism and transporter polymorphisms (AM) and (5) no mutations (Wild Type, WT). The percentage of the samples out of therapeutic range was significantly higher in the IM group than in the WT group (p = 0.001), as well as compared to the TM group (p = 0.004). Only IM pattern (p = 0.015) resulted as an independent predictor of number of tacrolimus blood levels out of therapeutic range. RM pattern (p = 0.006) was inversely related to the administered dose. Therefore, genotyping could become a standard practice before tacrolimus prescription thus decreasing side effects, increasing efficacy and reducing the economic burden for the national health system.

Clinical Outcome and Antimicrobial Therapeutic Drug Monitoring for the Treatment of Infections in Acute Burn Patients

2017 ◽  
Vol 39 (8) ◽  
pp. 1649-1657.e3 ◽  
Author(s):  
Anna Silva Machado ◽  
Maura S. Oliveira ◽  
Cristina Sanches ◽  
Carlindo Vieira da Silva Junior ◽  
David S. Gomez ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Clinical Outcome ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Burn Patients
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