scholarly journals Validation and Clinical Application of a New Liquid Chromatography Coupled to Mass Spectrometry (HPLC-MS) Method for Dalbavancin Quantification in Human Plasma

Separations ◽  
2021 ◽  
Vol 8 (10) ◽  
pp. 189
Author(s):  
Valeria Avataneo ◽  
Miriam Antonucci ◽  
Elisa Delia De De Vivo ◽  
Antonio Briozzo ◽  
Jessica Cusato ◽  
...  
Keyword(s):  
Renal Function ◽  
Human Plasma ◽  
Normal Renal Function ◽  
Extraction Procedure ◽  
Real Life ◽  
Therapeutic Drug ◽  
Continuous Hemodiafiltration ◽  
Positive Skin ◽  
High Doses ◽  
Long Acting

Dalbavancin (DBV) is an intravenous long-acting second-generation glycolipopeptide antibiotic with high efficacy and excellent tolerability, approved for use in the treatment of Gram-positive skin and skin structure infections (ABSSSI). Nevertheless, little is known about its pharmacokinetic/pharmacodynamic (PK/PD) properties in real life, which is also due to technical challenges in its quantification in human plasma, preventing an effective application of therapeutic drug monitoring (TDM). In fact, DBV has a high affinity to plasma proteins, possibly resulting in poor recovery after extraction procedure. The aim of this study was to validate a simple, cheap and reliable HPLC-MS method for use in TDM, in accordance with FDA and EMA guidelines. The optimized protein precipitation protocol required 50 μL of plasma, while chromatographic analysis could be performed in 12 min/sample. This method fulfilled the guidelines requirements and then, it was applied for routine DBV TDM in patients receiving off-label high doses (two 1500 + 1500 mg weekly infusions instead of 1000 + 500 mg), with normal renal function or undergoing hemodialysis: continuous hemodiafiltration caused a relevant reduction in DBV exposure, while intermittent dialysis showed comparable DBV concentrations with those of patients with normal renal function. This confirmed the eligibility of the presented method for use in TDM and its usefulness in clinical practice.

scholarly journals Long-acting antiretrovirals: a new era for the management and prevention of HIV infection

2021 ◽  
Author(s):  
Paul Thoueille ◽  
Eva Choong ◽  
Matthias Cavassini ◽  
Thierry Buclin ◽  
Laurent A Decosterd
Keyword(s):  
Hiv Infection ◽  
Drug Exposure ◽  
Real Life ◽  
Effective Vaccine ◽  
Therapeutic Drug ◽  
People Living With Hiv ◽  
Medical Procedure ◽  
Clinical Pharmacokinetics ◽  
Long Acting ◽  
Prevention Of Hiv

Abstract The long-acting antiretroviral cabotegravir and rilpivirine combination has just received FDA, EMA and Health Canada approval. This novel drug delivery approach is about to revolutionize the therapy of people living with HIV, decreasing the 365 daily pill burden to only six intramuscular injections per year. In addition, islatravir, a first-in-class nucleoside reverse transcriptase translocation inhibitor, is intended to be formulated as an implant with a dosing interval of 1 year or more. At present, long-acting antiretroviral therapies (LA-ARTs) are given at fixed standard doses, irrespectively of the patient’s weight and BMI, and without consideration for host genetic and non-genetic factors likely influencing their systemic disposition. Despite a few remaining challenges related to administration (e.g. pain, dedicated medical procedure), the development and implementation of LA-ARTs can overcome long-term adherence issues by improving patients’ privacy and reducing social stigma associated with the daily oral intake of anti-HIV treatments. Yet, the current ‘one-size-fits-all’ approach does not account for the recognized significant inter-individual variability in LA-ART pharmacokinetics. Therapeutic drug monitoring (TDM), an important tool for precision medicine, may provide physicians with valuable information on actual drug exposure in patients, contributing to improve their management in real life. The present review aims to update the current state of knowledge on these novel promising LA-ARTs and discusses their implications, particularly from a clinical pharmacokinetics perspective, for the future management and prevention of HIV infection, issues of ongoing importance in the absence of curative treatment or an effective vaccine.

Elevated Plasma Aluminum Levels in Normal Infants Receiving Antacids Containing Aluminum

PEDIATRICS ◽  
1991 ◽  
Vol 87 (2) ◽  
pp. 148-151
Author(s):  
V. Marc Tsou ◽  
Rose M. Young ◽  
Michael H. Hart ◽  
Jon A. Vanderhoof
Keyword(s):  
Renal Function ◽  
Plasma Level ◽  
Normal Renal Function ◽  
Aluminum Toxicity ◽  
Control Group ◽  
Elevated Plasma ◽  
Careful Monitoring ◽  
Aluminum Level ◽  
Aluminum Accumulation ◽  
High Doses

Aluminum toxicity is a documented cause of encephalopathy, anemia, and osteomalacia. Excretion is primarily renal; therefore, patients with renal insufficiency are at risk for aluminum accumulation and toxicity. This has been demonstrated in uremic children treated with aluminum-containing antacids. The purpose of this study was to determine whether plasma aluminum levels were elevated in infants with normal renal function during prolonged aluminum-containing antacid use. Ten study infants (mean age = 5.8 months), who had been receiving antacids for at least 1 week, were compared with 16 control infants (mean age = 9.8 months) not receiving antacids. The study patients consumed 123 ± 16 mg/kg per day (mean ± SEM) of elemental aluminum for an average of 4.7 weeks. Their plasma aluminum level (37.2 ± 7.13 µg/L) was significantly greater than that of the control group (4.13 ± 0.66 µg/L) (P < .005). It is concluded that plasma aluminum levels may become elevated in infants with normal renal function who are consuming high doses of aluminum-containing antacids. The safety of antacids containing aluminum should not be assumed and they should be used judiciously in infants, with careful monitoring of the aluminum dose and plasma level.

scholarly journals Pharmacokinetics of enalapril in patients with arterial hypertension depending on the glomerular filtration rate

2019 ◽  
Vol 10 (3) ◽  
pp. 37-41
Author(s):  
Marina V. Zhuravleva ◽  
Aleksei B. Prokofiev ◽  
Artem I. Dmitriev ◽  
Sergei A. Belkov ◽  
Evgenii S. Melnikov ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Arterial Hypertension ◽  
Drug Monitoring ◽  
Impaired Renal Function ◽  
Therapeutic Drug ◽  
Main Metabolite ◽  
High Prevalence ◽  
High Doses ◽  
Enalapril And Enalaprilat

Aim. To study the pharmacokinetics of enalapril in patients with arterial hypertension, depending on the value of the prescribed dose of enalapril and the state of renal function to improve the efficiency and safety of treatment. Materials and methods. The study was performed in a group of 328 patients (107 men and 221 women aged 43 to 88 years) who received treatment for hypertension of 1-2 degrees. As the main antihypertensive drug was prescribed enalapril in doses of 2.5 to 20 mg twice a day. Patients underwent therapeutic drug monitoring to determine the concentration of enalapril and its metabolite - enalaprilat. Results. Among the examined patients in 31% of cases there was a decrease in GFR less than 60 ml/min, and in 9 (3%) patients GFR was less than 30 ml/min. This indicates a high prevalence of chronic kidney disease among patients with hypertension. During therapeutic drug monitoring enalapril in patients with hypertension and reduced GFR (less than 60 ml/min) serum concentration of the main metabolite was 1.5-2 times higher than in patients with GFR more than 60 ml/min. Conclusion. It is advisable to carry out therapeutic drug monitoring to determine the concentrations of enalapril and enalaprilat in the serum of patients receiving the drug in high doses and having impaired renal function. In the appointment of enalapril in high doses to patients with reduced GFR, the concentration of enalaprilat significantly exceeds similar indicators in patients with normal GFR and in some cases goes beyond the therapeutic range, indicating the need to consider the correction of the treatment regimen.

scholarly journals Rivaroxaban dosing in patients with atrial fibrillation: results from the RIVER registry – is dosing according to renal function appropriate?

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.J Camm ◽  
S Virdone ◽  
K.A.A Fox ◽  
K.S Pieper ◽  
J Beyer-Westendorf ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Renal Impairment ◽  
Major Bleeding ◽  
Cardiovascular Mortality ◽  
Normal Renal Function ◽  
Severe Renal Impairment ◽  
Real Life ◽  
High Dose ◽  
The Impact

Abstract Introduction Rivaroxaban is recommended as an option for anticoagulation in patients with nonvalvular atrial fibrillation (AF) with one or more risk factors for stroke. The approved/recommended rivaroxaban dose for stroke prevention in patients with atrial fibrillation (AF) is solely based on renal function: 20 mg once daily (od) for patients with a creatinine clearance [CrCl] ≥50 ml/min and 15 mg od in patients with CrCl 15–49 mL/min). Purpose To assess the patterns of rivaroxaban prescription as per the creatinine clearances levels and to assess the impact of the rivaroxaban dosing on the rate of events at 2-year follow-up in patients with AF. Methods RIVaroxaban Evaluation in Real Life setting (RIVER) is a prospective international registry of patients with newly diagnosed non-valvular AF treated with rivaroxaban for the prevention of thromboembolic stroke and at least one investigator-determined risk factor for stroke. Adjusted hazard ratios (HRs) were obtained through Cox proportional-hazard model. Results Among 3402 patients with normal renal function (CrCl ≥50 mL/min), 82.1% were prescribed the recommended rivaroxaban dose of 20 mg (od) at baseline. Among 524 patients with moderate or severe renal impairment (CrCl 15–50 mL/min), 55.3% patients received rivaroxaban 15 mg (od), 39.9% received 20 mg (od) and 4.2% 10 mg (od). Non-recommended dosing was rare in patients younger than 70 (13.5%) but more frequent in older patients (28.8%). Non-recommended low dosing was more frequent in Asians (38.9%), compared to non-Asian patients (13.8%). Regarding clinical outcomes, adjusted hazards ratios (HR, presented with 95% confidence intervals) showed that the non-recommended low dosing (<20 mg od) was associated with higher risk of non-cardiovascular mortality (HR 2.09 (1.16–3.77)) in patients with normal renal function. The non-recommended high dosing (>15 mg od) was associated with lower risk of all-cause mortality (HR 0.63 (0.42–0.93)) and cardiovascular mortality (HR 0.32 (0.13–0.77)) and higher risk of major bleeding (HR 2.86 (1.49–5.50)) in patients with moderate to severe renal impairment (figure 1 and 2). Conclusion In patients with normal renal function, non-recommended low dose rivaroxaban was associated with increased cardiovascular mortality without reducing the risk of major bleeding compared to recommended dosing. In patients with CrCl <50 ml/min, non-recommended high dose rivaroxaban was associated with reduced cardiovascular mortality but at the cost of increased major bleeding. These observational data largely support the reduction of rivaroxaban dosing according to renal function but educational strategies are needed to ensure that rivaroxaban is used appropriately. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the RIVER registry. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

scholarly journals Pharmacokinetics of vancomycin in patients with different renal function levels

Open Medicine ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 512-519 ◽  
Author(s):  
Radica Zivkovic Zaric ◽  
Jasmina Milovanovic ◽  
Nikola Rosic ◽  
Dragan Milovanovic ◽  
Dejana Ruzic Zecevic ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Function ◽  
Normal Renal Function ◽  
Kidney Failure ◽  
Chronic Kidney Failure ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Final Model ◽  
Population Pharmacokinetic Modeling ◽  
High Doses

AbstractThere are many determinants of vancomycin clearance, but these have not been analyzed separately in populations with different levels of renal function, which could be why some important factors have been missed. The aim of our study was to compare the pharmacokinetic parameters and factors that may affect vancomycin pharmacokinetics in groups of patients with normal renal function and in those with chronic kidney failure. The study used a population pharmacokinetic modeling approach, based on plasma vancomycin concentrations and other data from 78 patients with chronic kidney failure and 32 patients with normal renal function. The model was developed using NONMEM software and validated by bootstrapping. The final model for patients with impaired kidney function was described by the following equation: CL (L/h) = 0.284 + 0.000596 x DD + 0.00194 x AST, and that for the patients with normal kidney function by: CL (L/h) = 0.0727 + 0.205 x FIB. If our results are confirmed by new studies on two similar populations, these factors could be considered when dosing vancomycin in patients with chronically damaged kidneys, as well as in patients with normal kidneys who frequently require high doses of vancomycin.

scholarly journals Dosing of Ertapenem in an Extreme Obesity: A Case Report of 250 kg Patient

2017 ◽  
Vol 2017 ◽  
pp. 1-3
Author(s):  
Jana Lass ◽  
Kadri Tamme ◽  
Karin Kipper ◽  
Joel Starkopf
Keyword(s):  
Renal Function ◽  
Case Report ◽  
Therapeutic Drug Monitoring ◽  
Normal Renal Function ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Extreme Obesity ◽  
Once Daily

Limited available data for dosing in obesity of the medicines used in this case are discussed, with the emphasis on ertapenem. The case illustrates the difficulties in dosing medicines to morbidly overweight patients. The number of such patients is increasing but data on adequate doses of medicines are scarce. We demonstrate that ertapenem 1,5 g i.v. once daily provided adequate drug exposure for susceptible bacteria in a 250 kg patient with normal renal function. The case suggests the usefulness of therapeutic drug monitoring of antibiotics, especially in critically ill patients.

scholarly journals A Simple Determination of Mizoribine in Human Plasma by Liquid Chromatography with UV Detection

2005 ◽  
Vol 88 (4) ◽  
pp. 1114-1117 ◽  
Author(s):  
Hiroaki Kaji ◽  
Takayoshi Maiguma ◽  
Yoko Inukai ◽  
Hiroshige Ono ◽  
Ritsuko Taniguchi ◽  
...  
Keyword(s):  
Renal Function ◽  
Liquid Chromatography ◽  
Human Plasma ◽  
Plasma Concentrations ◽  
Peak Height ◽  
Therapeutic Drug ◽  
Simple Liquid ◽  
Relative Standard ◽  
Limit Of Quantitation

Abstract A simple liquid chromatography (LC) method was developed for determination of the therapeutic level of mizoribine in human plasma. After precipitation of plasma proteins with 6% perchloric acid, mizoribine was determined by LC with spectophotometric detection. The peak height for mizoribine was linearly related to its concentrations, which ranged from 0.09 to 3.13 μg/mL. Therefore, the limit of quantitation was considered to be 0.09 μg/mL. The accuracy was 104.96–107.37%. The intra- and interday relative standard deviation values were in the range of 1.10–3.25%. The detection limit was 0.025 μ g/mL, defined as a signal-to-noise ratio of 3. The plasma concentrations of mioribine were not related to the dosage. Because mizoribine was mainly excreted in the urine, the plasma concentrations of mizoribine might be affected by a change in renal function. Therefore, the mizoribine concentration in blood should be monitored and the dosage adjusted, depending on the condition of renal function. It was suggested that the present method may be applied well in the therapeutic drug monitoring for mizoribine.

scholarly journals Population Pharmacokinetics of Emtricitabine in HIV-1-Infected Adult Patients

2014 ◽  
Vol 58 (4) ◽  
pp. 2256-2261 ◽  
Author(s):  
Elodie Valade ◽  
Jean-Marc Tréluyer ◽  
Naïm Bouazza ◽  
Jade Ghosn ◽  
Frantz Foissac ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Adult Patients ◽  
Moderate Renal Impairment ◽  
Therapeutic Drug ◽  
Parameter Estimates ◽  
Population Parameter ◽  
Concentration Time ◽  
Hiv 1

ABSTRACTThe aims of this study were to describe emtricitabine concentration-time courses in a large population of HIV-1-infected adults, to evaluate the influence of renal function on emtricitabine disposition, and to assess current dosing adjustment recommendations. Emtricitabine blood plasma concentrations were determined from samples collected from 161 adult patients during therapeutic drug monitoring and measured by liquid chromatography coupled to tandem mass spectrometry. The data were analyzed by a population approach. Emtricitabine pharmacokinetics was best described by a two-compartment model in which the absorption and distribution rate constants were assumed to be equal. Typical population parameter estimates (interindividual variability) were apparent elimination and intercompartmental clearances of 15.1 liters/h (17.4%) and 5.75 liters/h, respectively, and apparent central and peripheral volumes of distribution of 42.3 liters and 55.4 liters, respectively. The apparent elimination clearance was significantly related to creatinine clearance (CLCR), reflecting renal function. For 200 mg once a day (QD), the median area under the concentration-time curve over 24 h (AUC0-24) was 12.5 mg · h/liter for patients with normal renal function (CLCR, >80 ml/min), 14.7 mg · h/liter for patients with mild renal impairment (CLCR, 79 to 50 ml/min), and 17.9 mg · h/liter for patients with moderate renal impairment (CLCR, 49 to 30 ml/min). Simulations of the recommended dosing schemes for the oral solid form of emtricitabine (i.e., 200 mg per 48 h according to renal function) led to lower emtricitabine exposures for patients with moderate renal impairment (median AUC0-48, 17.2 mg · h/liter) than for patients with normal renal function (median AUC0-48, 25.6 mg · h/liter). Administering 18 ml of emtricitabine oral solution (10 mg/ml) QD to patients with moderate renal impairment should yield emtricitabine exposures similar to those in patients with normal renal function.

scholarly journals Effect of augmented renal clearance on the therapeutic drug monitoring of vancomycin in patients after neurosurgery

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052094907
Author(s):  
Yue Chen ◽  
Lei Liu ◽  
Man Zhu
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Renal Clearance ◽  
Normal Renal Function ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Augmented Renal Clearance ◽  
Achievement Rate ◽  
Baseline Characteristics

Objective To study the effect of augmented renal clearance (ARC) on vancomycin therapeutic drug monitoring in patients undergoing neurosurgery. Methods A retrospective observational analysis was conducted in a neurosurgery department from January 2019 to June 2019. Patients undergoing vancomycin therapeutic drug monitoring were assigned to the normal renal function or ARC group. The baseline characteristics, vancomycin therapeutic drug monitoring data, and prognosis were compared and analyzed. Results In total, 104 patients were enrolled, including 78 and 26 patients in the normal renal function and ARC groups, respectively. There were significant differences in age, weight, creatinine clearance, the vancomycin treatment duration, the total dose, the trough concentration, and the trough concentration achievement rate between the two groups. Prognosis did not differ between the two groups. The trough concentration achievement rate in the ARC group was only 19.23%. Conclusion For young, obese, or otherwise healthy patients undergoing neurosurgery, attention should be paid to the possibility of ARC and the need for individualized dose adjustment based on the results of therapeutic drug monitoring.

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