scholarly journals Population pharmacokinetic evaluation and optimization of amikacin dosage regimens for the management of mycobacterial infections

2020 ◽  
Vol 75 (10) ◽  
pp. 2933-2940
Author(s):  
Hinke Siebinga ◽  
Fiona Robb ◽  
Alison H Thomson
Keyword(s):  
Dose Adjustment ◽  
Population Pharmacokinetic ◽  
Limited Information ◽  
Once Daily ◽  
Mycobacterial Infections ◽  
Dosing Interval ◽  
Dosage Regimens ◽  
Population Pk ◽  
Post Infusion ◽  
Dosage Guidelines

Abstract Background There is limited information on amikacin pharmacokinetics (PK) and dose requirements in patients with mycobacterial infections. Objectives To conduct a population PK analysis of amikacin data from patients with mycobacterial infections and compare predicted concentrations from standard and modified dosage guidelines with recommended target ranges. Methods A population PK model was developed using NONMEM. Cmax, Cmin, concentration 1 h post-infusion (C1h) and AUC0–24 using 15 mg/kg daily (once daily), the WHO table, 25 mg/kg three times weekly (TTW) and modified guidelines were compared using Monte Carlo simulations of 1000 patients. Results Data were available from 124 patients (684 concentrations) aged 16–92 years. CL was 4.64 L/h per 100 mL/min CLCR; V was 0.344 L/kg. With once-daily regimens, Cmax was 35–45 mg/L in 30%–35% of patients and 35–50 mg/L in 46%–48%; C1h was 25–40 mg/L in 53%–59%. The WHO table produced high Cmax values in patients <60 kg and low in patients >75 kg. With TTW dosing, around 30% of Cmax values were 65–80 mg/L, 40% were 60–80 mg/L, and 48% of C1h were 45–65 mg/L. Increasing the dosage interval for patients with CLCR <50 mL/min reduced Cmin values >2 mg/L from 34% to 25% for once-daily dosing and from 18% to 13% for TTW. In patients whose Cmin was <2 mg/L, 82% of AUC0–24 values were 100–300 mg.h/L. Conclusions Standard amikacin dosing guidelines achieve low percentages of target concentrations for mycobacterial infections. Extending the dosing interval in renal impairment and widening target ranges would reduce the need for dose adjustment.

scholarly journals Bayesian forecasting for intravenous tobramycin dosing in adults with Cystic Fibrosis using one versus two serum concentrations in a dosing interval

2021 ◽  
Author(s):  
Philip G. Drennan ◽  
Yann Thoma ◽  
Lucinda Barry ◽  
Johan Matthey ◽  
Sheila Sivam ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Sampling Strategy ◽  
Prolonged Treatment ◽  
Accurate Estimation ◽  
Population Pharmacokinetic ◽  
List Type ◽  
Bayesian Forecasting ◽  
Concentration Data ◽  
Dosing Interval ◽  
Post Infusion

AbstractBackgroundIntravenous tobramycin requires therapeutic drug monitoring (TDM) to ensure safety and efficacy when used for prolonged treatment, as in infective exacerbations of Cystic Fibrosis (CF). The 24 hour area under the concentration time curve (AUC24) is widely used to guide dosing, however there remains variability in practice around methods for its estimation.ObjectivesTo determine the potential for a sparse sampling strategy using a single post-infusion tobramycin concentration and Bayesian forecasting, to assess the AUC24 in routine practice.MethodsAdults with CF receiving once daily tobramycin had paired concentrations measured 2 hours (c1) and 6 hours (c2) following end of infusion as routine monitoring. We estimated AUC24 exposures using Tucuxi, a Bayesian forecasting application incorporating a validated population pharmacokinetic model. We performed simulations to estimate AUC24 using the full dataset using c1 and c2, compared to estimates using depleted datasets (c1 or c2 only), with and without concentration data from earlier in the course. We assessed agreement between each simulation condition and the reference graphically, and numerically using median difference (Δ) AUC24, and (relative) root mean square error (rRMSE) as measures of bias and accuracy respectively.Results55 patients contributed 512 concentrations from 95 tobramycin courses and 256 TDM episodes. Single concentration methods performed well, with median ΔAUC24 <2 mg.h.l-1 and rRMSE of <15% for sequential c1 and c2 conditions.ConclusionsBayesian forecasting, using single post-infusion concentrations taken 2-6 hours following tobramycin administration can adequately estimate true exposure in this patient group and are suitable for routine TDM practice.Key Points-In stable adult patients with Cystic fibrosis without significant renal impairment, Bayesian forecasting allows accurate estimation of tobramycin AUC24 using a single blood sample taken 2-6 hours post-infusion with acceptable accuracy, especially when including prior measured concentrations.-A single sample approach with Bayesian forecasting is logistically less complicated than a two-sample approach, and could facilitate best-practice TDM in the outpatient setting.-A more intensive sampling strategy with Bayesian forecasting using two tobramycin concentrations in a dosing interval should be considered in unstable patients, or where observed concentrations deviate significantly from model predictions.

Use of a Population Pharmacokinetic Model of ADVATE In Pediatric and Adult Patients with Hemophilia A Permits Limited Blood Sampling for Individual Dose Tailoring.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1416-1416
Author(s):  
MyungShin Oh ◽  
Sven Björkman ◽  
Phillip Schroth ◽  
Sandor Fritsch ◽  
Peter W Collins ◽  
...  
Keyword(s):  
Body Weight ◽  
Hemophilia A ◽  
Volume Of Distribution ◽  
Sampling Time ◽  
Adult Patients ◽  
Population Pharmacokinetic ◽  
Data Sets ◽  
Time Points ◽  
Population Pk ◽  
Post Infusion

Abstract Abstract 1416 Introduction: A population pharmacokinetic (PK) model of a recombinant FVIII (rFVIII) was established on ADVATE® (Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method) studies in pediatric and adult patients with hemophilia A. The objective of this analysis was to evaluate the effect of reduced PK sampling time points on the estimated PK parameters in the population PK model. Patients and Methods: Plasma FVIII activity PK data were collected for 3 ADVATE® clinical trials in previously treated patients: 184 full PK data sets (11 time points) for 100 adults/adolescents, aged 10 to 65 years, and from 52 reduced sample PK data sets (5 time points) for 52 children, aged 1 to 6 years. A population PK analysis was conducted on a two-compartment structure model and the covariate effect of age and weight was explored. Four reduced sampling scenarios from the full 10 post-infusion sampling time points, were investigated: 1) Reduced to 4 (1 hr, 9 hr, 24 hr, and 48 hr), 2) Reduced to 3 (6 hr, 24 hr, and 48 hr), 3) Reduced to 2 (6 hr and 24 hr), and 4) Reduced to 1 sampling time points (24 hr post-infusion). After applying the reduced sampling on a random 10% of sampling set at a time in the population PK model, the differences in model estimates and individual PK estimates between full and reduced sampling, were evaluated. Results: The two-compartment population PK model adequately described the data. Clearance (CL) was significantly correlated with age and body weight and central volume of distribution was also related with body weight. Absolute deviations (%) from the estimates using full PK sampling in the Individual PK estimates (CL, Vss, and Half-life) using each of the reduced sampling time points were showed in the below table. Conclusions: It appears that PK parameters estimated using population PK model are robust to reduced sampling time points. Accurate measurement of PK on reduced samples gives patients and clinicians the opportunity to design treatment regimens that are better tailored to individuals. Disclosures: Oh: Baxter: Employment. Björkman:Baxter: Consultancy; Octapharma: Consultancy. Schroth:Baxter: Employment. Fritsch:Baxter: Employment. Collins:NovoNordisk: Consultancy, Honoraria, The EACH2 registry was funded by Novonordisk; Baxter Healthcare: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Fischer:Baxter: Consultancy; NovoNordisk: Consultancy. Blanchette:Bayer: Consultancy; Baxter: Research Support. Casey:Baxter: Employment. Spotts:Baxter: Employment. Ewenstein:Baxter Bioscience: Employment.

scholarly journals Target attainment of extended-interval dosing of tobramycin in patients less than five years of age with cystic fibrosis: A pharmacokinetic analysis.

2022 ◽  
Author(s):  
Kevin J Downes ◽  
Austyn Grim ◽  
Laura Shanley ◽  
Ronald C Rubenstein ◽  
Athena F Zuppa ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Young Patients ◽  
Therapeutic Targets ◽  
Compartment Model ◽  
Simulated Patients ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Once Daily ◽  
Therapeutic Goals ◽  
Population Pk

Background: Extended interval dosing (EID) of tobramycin is recommended for treatment of pulmonary exacerbations in adults and older children with cystic fibrosis (CF), but data are limited in patients less than 5 years of age.Methods:We performed a retrospective population pharmacokinetic (PK) analysis of hospitalized children with CF <5 years of age prescribed intravenous tobramycin for a pulmonary exacerbation from March 2011 to September 2018 at our hospital. Children with normal renal function who had ≥1 tobramycin concentration available were included. Nonlinear mixed effects population PK modeling was performed using NONMEM® using data from the first 48 hours of tobramycin treatment. Monte Carlo simulations were implemented to determine the fraction of simulated patients that met published therapeutic targets with regimens of 10-15 mg/kg/day once daily dosing. Results:Fifty-eight patients received 111 tobramycin courses (range 1-9/patient). A 2-compartment model best described the data. Age, glomerular filtration rate, and vancomycin coadministration were significant covariates on tobramycin clearance. The typical values of clearance and central volume of distribution were 0.252 L/hr/kg^0.75 and 0.308 L/kg, respectively. No once daily regimens achieved all pre-specified targets simultaneously in >75% of simulated subjects. A dosage of 13 mg/kg/dose best met the predefined targets of Cmax >25 mg/L and AUC24 of 80-120 mg*h/L.Conclusions:Based on our population PK analysis and simulations, once daily dosing of tobramycin would not achieve all therapeutic goals in young patients with CF. However, extended-interval dosing regimens may attain therapeutic targets in the majority of young patients.

scholarly journals A Population Pharmacokinetic Model for Concizumab Based on Phase 1 and Phase 2 Trial Data

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-4
Author(s):  
Trine Høyer Rose ◽  
Christian Hollensen ◽  
Henrik Agersø ◽  
Rune Viig Overgaard
Keyword(s):  
Rate Constant ◽  
Drug Disposition ◽  
Hemophilia A ◽  
Phase 1 ◽  
Population Pharmacokinetic ◽  
Phase 2 ◽  
Publicly Traded ◽  
Phase 3 ◽  
Target Mediated Drug Disposition ◽  
Population Pk

Introduction Concizumab is a high-affinity anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody in clinical investigation for the subcutaneous (SC) treatment of patients with hemophilia. The data generated from phase 1 and 2 concizumab trials have been used to develop a population pharmacokinetic (PK) model with the aim of supporting dose selection for phase 3 trials. WMethods The objective of this study was to develop a model to describe the PK of concizumab across administration routes in various groups of patients with hemophilia to generate a generally applicable population PK model of concizumab. The model was developed based on available PK data from four phase 1 trials (for both intravenous [IV] and SC concizumab administration) and two phase 2 trials (for SC concizumab administration). Trial populations in the phase 1 trials included both healthy subjects and patients with hemophilia, whilst the phase 2 trials enrolled patients with hemophilia A or B with inhibitors and patients with hemophilia A without inhibitors. A structural population PK model was first developed based on phase 1 data and the final population PK model was then estimated using data from both phase 1 and phase 2 trials. Simulations were performed for phase 3 concizumab exposure using a full parametric simulation (n=10,000), including both inter-individual and intra-individual variability for the selected population. Randomly sampled body weights from a normal distribution with mean and variance corresponding to body weight distribution from phase 2 trials were used to simulate patient profiles. WResults The population PK dataset used for the model comprised 1,504 observations from 119 subjects (89 patients and 30 healthy individuals), with a mean age of 35 years (range: 18-65 years) and mean body weight of 74.4 kg (range: 47.1-130 kg). The PK model parameters were first estimated based on phase 1 data alone, and after fixing the majority in order to ensure robustness of the model only a few parameters were re-estimated based on phase 1 and 2 data combined. The PK model (Figure 1) was evaluated by standard goodness-of-fit plots and qualification assessments. Using visual predictive checks, it was shown that the model was able to reproduce the median and the 5th and 95th percentiles of the observed concizumab concentrations from phase 1 and 2 trials, and so it was deemed suitable for simulation purposes. The PK model suggested a target-mediated drug disposition following concizumab binding to TFPI at the endothelium, and subsequent elimination of the complex to account for the non-linear elimination. WConclusions The developed model accurately described the PK of concizumab delivered at a wide dose range by either SC or IV administration to both healthy subjects and patients with hemophilia A or B with and without inhibitors. The model was used for simulations to select the dosing regimen for subsequent phase 3 studies. Figure 1. Concizumab pharmacokinetic model. Structure of the final concizumab PK model for SC and IV dosing with target-mediated drug disposition via the endothelial TFPI. CL, clearance; doseiv, intravenous dose; dosesc, subcutaneous dose; IV, intravenous; ka, absorption rate constant; kcom, elimination rate constant of the concizumab-TFPI complex; kon and koff, rate constants for binding of concizumab to the endothelial TFPI; ktr, rate constant from the transit compartment; Q, inter-compartmental clearance; Rtot, amount of endothelial TFPI available for concizumab binding; SC, subcutaneous; TFPI, tissue factor pathway inhibitor; V, volume. Figure Disclosures Høyer Rose: Novo Nordisk A/S: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Hollensen:Novo Nordisk: Current Employment, Current equity holder in private company, Current equity holder in publicly-traded company. Agersø:Novo Nordisk A/S: Current Employment. Viig Overgaard:Novo Nordisk A/S: Current Employment, Current equity holder in publicly-traded company.

scholarly journals Evaluation of the Adequacy of WHO Revised Dosages of the First-Line Antituberculosis Drugs in Children with Tuberculosis Using Population Pharmacokinetic Modeling and Simulations

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Yasuhiro Horita ◽  
Abdullah Alsultan ◽  
Awewura Kwara ◽  
Sampson Antwi ◽  
Antony Enimil ◽  
...  
Keyword(s):  
Compartment Model ◽  
World Health ◽  
Population Pharmacokinetic ◽  
Optimal Dosage ◽  
Nonlinear Mixed Effects Models ◽  
First Line ◽  
Time Curve ◽  
Drug Concentrations ◽  
Target Values ◽  
Population Pk

ABSTRACTOptimal doses for antituberculosis (anti-TB) drugs in children have yet to be established. In 2010, the World Health Organization (WHO) recommended revised dosages of the first-line anti-TB drugs for children. Pharmacokinetic (PK) studies that investigated the adequacy of the WHO revised dosages to date have yielded conflicting results. We performed population PK modeling using data from one of these studies to identify optimal dosage ranges. Ghanaian children with tuberculosis on recommended therapy with rifampin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods. Nonlinear mixed-effects models were applied to describe the population PK of those drugs using MonolixSuite2016R1 (Lixoft, France). Bayesian estimation was performed, the correlation coefficient, bias, and precision between the observed and predicted areas under the concentration-time curve (AUCs) were calculated, and Bland-Altman plots were analyzed. The population PK of RIF and PZA was described by a one-compartment model and that for INH and EMB by a two-compartment model. Plasma maximum concentration (Cmax) and AUC targets were based on published results for children from India. The lowest target values for pediatric TB patients were attainable at the WHO-recommended dosage schedule for RIF and INH, except forN-acetyltransferase 2 non-slow acetylators (rapid and intermediate acetylators) in the lower-weight bands. However, higher published adult targets were not attainable for RIF and INH. The targets were not achieved for PZA and EMB. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.)

Population pharmacokinetic modeling and dosing simulations of tobramycin in pediatric patients with cystic fibrosis

2021 ◽  
Author(s):  
Antonin Praet ◽  
Laurent Bourguignon ◽  
Florence Vetele ◽  
Valentine Breant ◽  
Charlotte Genestet ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Dose Adjustment ◽  
Total Body Weight ◽  
Compartment Model ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Population Pharmacokinetic Modeling ◽  
Two Compartment Model ◽  
Total Body

Initial dosing and dose adjustment of intravenous tobramycin in cystic fibrosis children is challenging. The objectives of this study were to develop nonparametric population pharmacokinetic (PK) models of tobramycin in children with CF to be used for dosage design and model-guided therapeutic drug monitoring. We performed a retrospective analysis of tobramycin PK data in our CF children center. The Pmetrics package was used for nonparametric population PK analysis and dosing simulations. Both the maximal concentration over the MIC (Cmax/MIC) and daily area under the concentration-time curve to the MIC (AUC 24 /MIC) ratios were considered as efficacy target. Trough concentration (Cmin) was considered as the safety target. A total of 2884 tobramycin concentrations collected in 195 patients over 9 years were analyzed. A two-compartment model including total body weight, body surface area and creatinine clearance as covariates best described the data. A simpler model was also derived for implementation into the BestDose software to perform Bayesian dose adjustment. Both models were externally validated. PK/PD simulations with the final model suggest that an initial dose of tobramycin of 15 to 17.5 mg/kg/day was necessary to achieve Cmax/MIC ≥ 10 values for MIC values up to 2 mg/L in most patients. The AUC 24 /MIC target was associated with larger dosage requirements and higher Cmin. A daily dose of 12.5 mg/kg would optimize both efficacy and safety target attainment. We recommend to perform tobramycin TDM, model-based dose adjustment, and MIC determination to individualize intravenous tobramycin therapy in children with CF.

scholarly journals Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Simulation of Piperacillin/Tazobactam for Dosing Optimization in Late Elderly Patients with Pneumonia

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 113 ◽  
Author(s):  
Noriyuki Ishihara ◽  
Nobuhiro Nishimura ◽  
Kazuro Ikawa ◽  
Fumi Karino ◽  
Kiyotaka Miura ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Elderly Patients ◽  
Distribution Volume ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Target Attainment ◽  
Old Patients ◽  
Final Model ◽  
Concentration Time ◽  
Population Pk

The aim of this study was to develop a population pharmacokinetic model for piperacillin (PIPC)/tazobactam (TAZ) in late elderly patients with pneumonia and to optimize the administration planning by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. PIPC/TAZ (total dose of 2.25 or 4.5 g) was infused intravenously three times daily to Japanese patients over 75 years old. The plasma concentrations of PIPC and TAZ were determined using high-performance liquid chromatography and modeled using the NONMEM program. PK/PD analysis with a random simulation was conducted using the final population PK model to estimate the probability of target attainment (PTA) profiles for various PIPC/TAZ-regimen–minimum-inhibitory-concentration (MIC) combinations. The PTAs for PIPC and TAZ were determined as the fraction that achieved at least 50% free time > MIC and area under the free-plasma-concentration–time curve over 24 h ≥ 96 μg h/mL, respectively. A total of 18 cases, the mean age of which was 86.5 ± 6.0 (75–101) years, were investigated. The plasma-concentration–time profiles of PIPC and TAZ were characterized by a two-compartment model. The parameter estimates for the final model, namely the total clearance, central distribution volume, peripheral distribution volume, and intercompartmental clearance, were 4.58 + 0.061 × (CLcr − 37.4) L/h, 5.39 L, 6.96 L, and 20.7 L/h for PIPC, and 5.00 + 0.059 × (CLcr − 37.4) L/h, 6.29 L, 7.73 L, and 24.0 L/h for TAZ, respectively, where CLcr is the creatinine clearance. PK/PD analysis using the final model showed that in drug-resistant strains with a MIC > 8 μg/mL, 4.5 g of PIPC/TAZ every 6 h was required, even for the patients with a CLcr of 50–60 mL/min. The population PK model developed in this study, together with MIC value, can be useful for optimizing the PIPC/TAZ dosage in the over-75-year-old patients, when they are administered PIPC/TAZ. Therefore, the findings of present study may contribute to improving the efficacy and safety of the administration of PIPC/TAZ therapy in late elderly patients with pneumonia.

scholarly journals Population Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Analyses of Cefiderocol, a Parenteral Siderophore Cephalosporin, in Patients with Pneumonia, Bloodstream Infection/Sepsis, or Complicated Urinary Tract Infection

2020 ◽  
Author(s):  
Nao Kawaguchi ◽  
Takayuki Katsube ◽  
Roger Echols ◽  
Toshihiro Wajima
Keyword(s):  
Urinary Tract Infection ◽  
Renal Function ◽  
Urinary Tract ◽  
Tract Infection ◽  
Bloodstream Infection ◽  
Plasma Concentrations ◽  
Complicated Urinary Tract Infection ◽  
Population Pharmacokinetic ◽  
Dosing Regimen ◽  
Population Pk

Cefiderocol is a novel siderophore cephalosporin with antibacterial activity against Gramnegative bacteria including carbapenemresistant strains. The standard dosing regimen of cefiderocol is 2 g administered every 8 hours over 3 hours infusion in patients with creatinine clearance (CrCL) of 60 to 119 mL/min, and it is adjusted for patients with < 60 mL/min or ≥ 120 mL/min CrCL. A population pharmacokinetic (PK) model was constructed using 3427 plasma concentrations from 91 uninfected subjects and 425 infected patients with pneumonia, bloodstream infection/sepsis (BSI/sepsis), and complicated urinary tract infection (cUTI). Plasma cefiderocol concentrations were adequately described by the population PK model, and CrCL was the most significant covariate. No other factors including infection sites and mechanical ventilation were clinically relevant, although the effect of infection sites was identified as a statistically significant covariate in the population PK analysis. No clear pharmacokinetic/pharmacodynamic relationship was found for any of the microbiological outcome, clinical outcome, or vital status. This is because the estimated percentage of time for which free plasma concentrations exceed the minimum inhibitory concentration (MIC) over dosing interval (%fT>MIC) was 100% in most of the enrolled patients. The probability of target attainment (PTA) for 100% fT>MIC was > 90% against MICs ≤ 4 μg/mL for all infection sites and renal function groups except for BSI/sepsis patients with normal renal function (85%). These study results support adequate plasma exposure can be achieved at the cefiderocol recommended dosing regimen for the infected patients including the patients with augmented renal function, ventilation, and/or severe illness.

Is the subcutaneous route an alternative for administering ertapenem to older patients? PHACINERTA study

2019 ◽  
Vol 74 (12) ◽  
pp. 3546-3554 ◽  
Author(s):  
Claire Roubaud Baudron ◽  
Rachel Legeron ◽  
Julien Ollivier ◽  
Fabrice Bonnet ◽  
Carine Greib ◽  
...  
Keyword(s):  
Older Patients ◽  
Older Persons ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Antibiotic Administration ◽  
Subcutaneous Route ◽  
Final Model ◽  
Once Daily ◽  
The Mean ◽  
Pharmacodynamic Data

Abstract Background Antibiotic administration by subcutaneous (SC) injection is common practice in French geriatric wards as an alternative to the intravenous (IV) route, but few pharmacokinetic/pharmacodynamic data are available. Ertapenem is useful for the treatment of infections with ESBL-producing enterobacteria. Objectives To report and compare ertapenem pharmacokinetic data between IV and SC routes in older persons. Methods Patients >65 years of age receiving ertapenem (1 g once daily) for at least 48 h (IV or SC, steady-state) were prospectively enrolled. Total ertapenem concentrations [residual (C0), IV peak (C0.5) and SC peak (C2.5)] were determined by UV HPLC. Individual-predicted AUC0–24 values were calculated and population pharmacokinetic analyses were performed. Using the final model, a Monte Carlo simulation involving 10 000 patients evaluated the influence of SC or IV administration on the PTA. Tolerance to ertapenem and recovery were also monitored. ClinicalTrials.gov identifier: NCT02505386. Results Ten (mean ± SD age=87±7 years) and 16 (age=88±5 years) patients were included in the IV and SC groups, respectively. The mean C0 and C2.5 values were not significantly different between the IV and SC groups (C0=12±5.9 versus 12±7.4 mg/L, P=0.97; C2.5=97±42 versus 67±41 mg/L, P=0.99). The mean C0.5 was higher in the IV group compared with the SC group (C0.5=184±90 versus 51±66 mg/L, P=0.001). The mean individual AUCs (1126.92±334.99 mg·h/L for IV versus 1005.3±266.0 mg·h/L for SC, P=0.38) and PTAs were not significantly different between groups. No severe antibiotic-related adverse effects were noted. Conclusions SC administration of ertapenem is an alternative to IV administration in older patients.

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