Pharmacokinetics and Pharmacodynamics of Linezolid in Patients With Sepsis Receiving Continuous Venovenous Hemofiltration and Extended Daily Hemofiltration

2020 ◽  
Vol 221 (Supplement_2) ◽  
pp. S279-S287
Author(s):  
Junbo Zheng ◽  
Zhidan Sun ◽  
Lei Sun ◽  
Xing Zhang ◽  
Guiying Hou ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Inhibitory Concentration ◽  
Compartment Model ◽  
Blood Levels ◽  
Continuous Venovenous Hemofiltration ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Target Attainment ◽  
Blood Samples ◽  
Failure Assessment

Abstract Background This prospective study compared pharmacokinetics (PK) and pharmacodynamics (PD) of linezolid in patients with sepsis receiving continuous venovenous hemofiltration (CVVH) with patients receiving extended daily hemofiltration (EDH). Methods Patients with sepsis treated with linezolid and CVVH or EDH were included. Serial blood samples were collected and linezolid concentrations measured. PKs were analyzed using Pmetrics. Monte Carlo simulations were used to evaluate PD target achievement. Results From 20 patients, 320 blood samples were collected for PK and PD analysis. PK profiles of linezolid were best described by a 2-compartment model. PK parameters were not significantly different between EDH and CVVH groups and were associated with body weight, renal replacement therapy (RRT) duration, and sequential organ failure assessment score. Monte Carlo simulations showed poor fractional target attainment for a minimum inhibitory concentration (MIC) of 2 mg/L with standard 600 mg intravenous administration every 12 hours. Conclusions Patients with sepsis receiving RRT exhibited variability in PK/PD parameters for linezolid. PK parameters were not significantly different between CVVH- and EDH-treated patients. Higher probability of target attainment would be achievable at a MIC of 2 mg/L in EDH patients. Higher linezolid doses should be considered for patients on RRT to achieve adequate blood levels.

scholarly journals Evaluating Ciprofloxacin Dosing for Pseudomonas aeruginosa Infection by Using Clinical Outcome-Based Monte Carlo Simulations

2005 ◽  
Vol 49 (10) ◽  
pp. 4009-4014 ◽  
Author(s):  
Sheryl Zelenitsky ◽  
Robert Ariano ◽  
Godfrey Harding ◽  
Alan Forrest
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Monte Carlo ◽  
Clinical Outcome ◽  
Monte Carlo Simulations ◽  
Standard Dose ◽  
High Dose ◽  
Target Attainment ◽  
Real Patient ◽  
Dosing Regimens ◽  
Cure Rates

ABSTRACT Pseudomonas aeruginosa causes serious infections whose outcome is highly dependent on antimicrobial therapy. The goal of this study was to predict the relative efficacies of three ciprofloxacin dosing regimens for P. aeruginosa infection using clinical outcome-based Monte Carlo simulations (MCS) with “real patient” demographics, pharmacokinetics, MICs, and pharmacodynamics (PDs). Each cohort consisted of 1,000 simulated study subjects. Three ciprofloxacin dosing regimens were studied, including (i) the recommended standard dose of 400 mg given intravenously (i.v.) every 12 h (q12h), (ii) the recommended high dose of 400 mg i.v. q8h, and (iii) a novel, PD-targeted regimen to attain a ƒAUC/MIC value of >86. Probability of target attainment (PTA) and probability of cure (POC) were determined for each regimen. POC with the standard dose was at least 0.90 if pathogen MICs were ≤0.25 μg/ml but only 0.59 or 0.27 if MICs were 0.5 or 1 μg/ml, respectively. Predicted cure rates in these MIC categories were significantly higher at 0.72 and 0.40 with the high dose and 0.91 and 0.72 with the PD-targeted regimen(P < 0.0001). Analyses based on the local susceptibility profile produced PTA and POC estimates of 0.44 and 0.74 with the standard ciprofloxacin dose, 0.58 and 0.81 with the high dose, and 0.84 and 0.93 with the PD-targeted regimen, respectively. In conclusion, as demonstrated by clinical outcome-based MCSs, the highest recommended ciprofloxacin dose of 400 mg i.v. q8h should be used in the treatment of P. aeruginosa infection to improve PD target attainment and clinical cure. However, even this appears ineffective if pathogen MICs are 1 μg/ml, warranting the consideration of a lower MIC breakpoint, ≤0.5 μg/ml.

scholarly journals Pharmacokinetics, Pharmacodynamic Efficacy Prediction Indexes and Monte Carlo Simulations of Enrofloxacin Hydrochloride Against Bacterial Strains That Induce Common Clinical Diseases in Broiler Chickens

2021 ◽  
Vol 7 ◽  
Author(s):  
Karina P. D. Bonassa ◽  
Miwa Y. Miragliotta ◽  
Rosineide C. Simas ◽  
Marcos N. Eberlin ◽  
Arturo Anadón ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Plasma Concentration ◽  
Monte Carlo Simulations ◽  
Broiler Chickens ◽  
Inhibitory Concentration ◽  
Plasma Concentrations ◽  
Bacterial Strains ◽  
E Coli ◽  
Concentration Time ◽  
Efficacy Prediction

Pharmacokinetic parameters and efficacy prediction indexes (Cmax/MIC90 and AUC0−24/MIC90) of an enrofloxacin hydrochloride (ENR-HCl) veterinary product soluble in water were determined in healthy broiler chickens of both sexes after a single oral dose of ENR-HCl (equivalent to 10 mg ENR base/kg bw). Monte Carlo simulations targeting Cmax/MIC90 = 10 and AUC0−24/MIC90 =125 were also performed based on a set of MIC (minimum inhibitory concentration) values of bacterial strains that induce common clinical diseases in broiler chickens and that showed to be susceptible to ENR-HCl. Plasma concentrations of ENR and its main metabolite ciprofloxacin (CIP) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma concentration-time curves were found to fit a non-compartmental open model. The ratio of the area under the plasma concentration-time curve (AUC) of CIP/ENR was 4.91%. Maximum plasma concentrations of 1.35 ± 0.15 μg/mL for ENR-HCl and 0.09 ± 0.01 μg/mL for CIP were reached at 4.00 ± 0.00 h and 3.44 ± 1.01 h, respectively. Areas under the plasma vs. time concentration curve in 24 h (AUC0−24) were 18.91 ± 1.91 h × μg/mL and 1.19 ± 0.12 h × μg/mL for ENR-HCl and CIP, respectively. Using a microbroth dilution method, the minimum inhibitory concentration (MIC90) values were determined for ENR-HCl for 10 bacterial strains (Mycoplasma gallisepticum, Mycoplasma synoviae, Avibacterium paragallinarum, Clostridium perfringens, Escherichia coli, Pseudomonas aeruginosa, Salmonella ser. Enteritidis, Salmonella ser. Gallinarum, Salmonella ser. Pullorum, and Salmonella ser. Typhimurium), which are the most common causes of infectious clinical diseases in broiler chickens. In summary, the PK/PD ratios and Monte Carlo simulation were carried out for ENR-HCl in poultry, which due to its solubility was administered in drinking water. The PK/PD efficacy prediction indexes and Monte Carlo simulations indicated that the ENR-HCl oral dose used in this study is useful for bacterial infections in treating C. perfringens (Gram-positive), E. coli and S. ser. Enteritidis (Gram-negative) and M. gallisepticum bacteria responsible for systemic infections in poultry, predicting a success rate of 100% when MIC ≤ 0.06 μg/mL for E. coli and S. ser. Enteritidis and MIC ≤ 0.1 μg/mL for M. gallisepticum. For C. perfringens, the success rate was 98.26% for MIC ≤ 0.12. However, clinical trials are needed to confirm this recommendation.

scholarly journals Cycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with Tuberculosis

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Wael A. Alghamdi ◽  
Abdullah Alsultan ◽  
Mohammad H. Al-Shaer ◽  
Guohua An ◽  
Shahriar Ahmed ◽  
...  
Keyword(s):  
Drug Effects ◽  
Compartment Model ◽  
Total Daily Dose ◽  
Drug Resistant ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Target Attainment ◽  
Data Set ◽  
Population Pk ◽  
Daily Dose ◽  
Insight Into

ABSTRACT Limited pharmacokinetic/pharmacodynamic (PK/PD) data exist on cycloserine in tuberculosis (TB) patients. We pooled several studies into a large PK data set to estimate the population PK parameters for cycloserine in TB patients. We also performed simulations to provide insight into optimizing the dosing of cycloserine. TB patients were included from Georgia, Bangladesh, and four U.S. sites. Monolix and mlxR package were used for population PK modeling and simulation. We used PK/PD targets for time above MIC of ≥30% and ≥64%, representing bactericidal activity and 80% of the maximum kill, to calculate the probability of target attainment (PTA). Optimal PK/PD breakpoints were defined as the highest MIC to achieve ≥90% of PTA. Data from 247 subjects, including 205 patients with drug-resistant TB, were included. The data were best described by a one-compartment model. In most cases, the PK/PD breakpoints for the simulated regimens were similar for both PK/PD targets. Higher PTA were achieved as the total daily dose was increased. The highest PK/PD breakpoint that resulted from the use of 250 mg dosages was 16 mg/liter. For MICs of >16 mg/liter, doses of at least 500 mg three times daily or 750 mg twice daily were needed. In conclusion, the current dosing for cycloserine, 250 to 500 mg once or twice daily, is not sufficient for MICs of >16mg/liter. Further studies are needed regarding the efficacy and tolerability of daily doses of >1,000 mg. Dividing the dose minimally affected the PK/PD breakpoints while optimizing exposure, which can potentially reduce adverse drug effects.

Simplifying Piperacillin/Tazobactam Dosing: Pharmacodynamics of Utilizing Only 4.5 or 3.375 g Doses for Patients With Normal and Impaired Renal Function

2016 ◽  
Vol 30 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Abrar K. Thabit ◽  
Mordechai Grupper ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Renal Function ◽  
Impaired Renal Function ◽  
Inhibitory Concentration ◽  
Prolonged Infusion ◽  
Target Attainment ◽  
Dosing Regimens ◽  
Function Range ◽  
Prescribing Information

Objectives: To evaluate the pharmacodynamic exposure of piperacillin/tazobactam across the renal function range using 4.5 or 3.375 g dosing regimens. Methods: A 5000-patient Monte Carlo simulation was conducted to determine the probability of achieving 50% free time above the minimum inhibitory concentration ( fT > MIC) for piperacillin. Proposed regimens, using solely 4.5 or 3.375 g strengths, were compared with regimens listed in piperacillin/tazobactam prescribing information over creatinine clearance (CrCl) ranges of 120 mL/min to hemodialysis. The probability of target attainment (PTA) at MICs ≤ 16 μg/mL was compared between proposed and standard regimens. Results: At CrCl 41 to 120 mL/min, prolonged infusions of 4.5 g (3 hours) and 3.375 g (4 hours) every 6 hours resulted in ≥95% PTA versus ≥76% for standard regimens (0.5 hour). At CrCl 20 to 40 mL/min, 4.5 and 3.375 g every 8 hours as prolonged infusions achieved slightly higher PTA (≥98%) versus standard regimens (≥93%). Similarly, PTA achieved with prolonged infusions of 4.5 and 3.375 g every 12 hours (≥93%) was comparable with those of standard regimens (≥91%) at CrCl 1 to 19 mL/min. In hemodialysis, 100% PTA was achieved with prolonged infusion regimens. Conclusion: Piperacillin/tazobactam regimens designed around the 4.5 or 3.375 g dose and prolonged infusions provided similar or better PTA at MICs ≤ 16 μg/mL compared with standard regimens. These observations may support the stocking and use of a single piperacillin/tazobactam strength to simplify dosing.

scholarly journals Optimizing gentamicin dosing in different pediatric age groups using population pharmacokinetics and Monte Carlo simulation

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Ragia H. Ghoneim ◽  
Abrar K. Thabit ◽  
Manar O. Lashkar ◽  
Ahmed S. Ali
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Population Pharmacokinetics ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic ◽  
Target Attainment ◽  
Concentration Data ◽  
Once Daily ◽  
Dosing Regimens ◽  
Gentamicin Concentration

Abstract Introduction The use of once daily dosing of aminoglycosides in pediatrics is increasing but studies on dose optimization targeting the pediatric population are limited. This study aimed to derive a population pharmacokinetic model of gentamicin and apply it to design optimal dosing regimens in pediatrics. Methods Population pharmacokinetics of gentamicin in pediatrics was described from a retrospective chart review of plasma gentamicin concentration data (peak/ trough levels) of pediatric patients (1 month − 12 years), admitted to non-critically ill pediatrics. Monte Carlo simulations were performed on the resulting pharmacokinetic model to assess the probability of achieving a Cmax/MIC target of 10 mg/L over a range of gentamicin MICs of 0.5–2 mg/L and once daily gentamicin dosing regimens. Results: A two-compartment model with additive residual error best described the model with weight incorporated as a significant covariate for both clearance and volume of distribution. Monte Carlo simulations demonstrated a good probability of target attainment even at a MIC of 2 mg/L, where neonates required doses of 6-7 mg/kg/day and older pediatrics required lower daily doses of 4–5 mg/kg/day while maintaining trough gentamicin concentration below the toxicity limit of 1 mg/L. Conclusion: Once daily dosing is a reasonable option in pediatrics that allows target attainment while maintaining trough gentamicin level below the limits of toxicity.

scholarly journals Pharmacokinetics and Pharmacodynamics of Linezolid following Intragastric and Intravenous Administrations in ICU Patients

2020 ◽  
Author(s):  
Zhidan Sun ◽  
Xing Zhang ◽  
Junbo Zheng ◽  
Guiying Hou ◽  
Qiuyuan Han ◽  
...  
Keyword(s):  
Body Weight ◽  
Sofa Score ◽  
Inhibitory Concentration ◽  
Liquid Volume ◽  
Lower Probability ◽  
Intragastric Administration ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Target Attainment ◽  
Standard Regimen ◽  
Linezolid Therapy

Abstract Background. Though intravenous infusion linezolid therapy is common for patients in the intensive care unit (ICU), intragastric linezolid therapy is also provided for those whose gastrointestinal function are feasible. If intragastric linezolid acquired similar pharmacokinetics (PK) and pharmacodynamics (PD) parameters, this might be preferred based on cost and ease of liquid volume management.Methods. Patients in the ICU treated with intragastric and intravenous linezolid were included. Serial blood samples were collected and linezolid concentrations were measured. PK data were analyzed using Pmetrics. Monte Carlo simulations were used to evaluate PD target achievement. Results. Tmax was 1.06 ± 0.82 h of the study period in 10 patients receiving intragastric linezolid and 0.65 ± 0.24 h in 10 patients receiving intravenous linezolid (p<0.001). Cmax was 9.07 ± 4.99 mg/mL of patients with intragastric linezolid and 12.30 ± 4.06 mg/mL of patients with intravenous linezolid (p=0.904). Clearance was 11.99 ± 11.24 L/h in patients with intragastric linezolid and 14.48 ± 3.56 L/h in patients with intravenous linezolid (p=0.342). For infections with a microorganism with a minimum inhibitory concentration (MIC) of 2 mg/L, simulations demonstrated that with 600 mg every 12 hours, 58.22% would have a linezolid concentration greater than the MIC during 100% of the dosing interval (%T > MIC = 100%) in intragastric group, whereas this was 71.36% in intravenous group. Higher SOFA score and body weight were associated with lower probability of target attainment (PTA) of linezolid with standard regimen.Conclusions. Patients in ICU may be at high risk for underexposure to linezolid by intragastric administration, especially when their SOFA score and body weight is high and when infected with pathogens with an MIC ≥ 2 mg/L.

scholarly journals Development of a Tracer Kinetic Plasma Input Model for (R)-[11C]PK11195 Brain Studies

2005 ◽  
Vol 25 (7) ◽  
pp. 842-851 ◽  
Author(s):  
Marc A Kropholler ◽  
Ronald Boellaard ◽  
Alie Schuitemaker ◽  
Bart NM van Berckel ◽  
Gert Luurtsema ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Benzodiazepine Receptor ◽  
Compartment Model ◽  
Input Function ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Arterial Blood ◽  
Tracer Kinetic ◽  
Input Model

(R)-[11C]PK11195 ([1-(2-chlorophenyl)- N-methyl- N-(1-methylpropyl]-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor, which, in the brain, is mainly expressed on activated microglia. Using both clinical studies and Monte Carlo simulations, the aim of this study was to determine which tracer kinetic plasma input model best describes (R)-[11C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were performed on 13 subjects while radioactivity in arterial blood was monitored online. Discrete blood samples were taken to generate a metabolite corrected plasma input function. One-tissue, two-tissue irreversible, and two-tissue reversible compartment models, with and without fixing K1/ k2 ratio, k4 or blood volume to whole cortex values, were fitted to the data. The effects of fixing parameters to incorrect values were investigated by varying them over a physiologic range and determining accuracy and reproducibility of binding potential and volume of distribution using Monte Carlo simulations. Clinical data showed that a two-tissue reversible compartment model was optimal for analyzing (R)-[11C]PK11195 PET brain studies. Simulations showed that fixing the K1/ k2 ratio of this model provided the optimal trade-off between accuracy and reproducibility. It was concluded that a two-tissue reversible compartment model with K1/ k2 fixed to whole cortex value is optimal for analyzing (R)-[11C]PK11195 PET brain studies.

scholarly journals Optimizing ethambutol dosing among HIV/tuberculosis co-infected patients: a population pharmacokinetic modelling and simulation study

2019 ◽  
Vol 74 (10) ◽  
pp. 2994-3002
Author(s):  
Krina Mehta ◽  
Shruthi Ravimohan ◽  
Jotam G Pasipanodya ◽  
Shashikant Srivastava ◽  
Chawangwa Modongo ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Oral Bioavailability ◽  
Population Pharmacokinetic ◽  
High Risk Population ◽  
Serum Concentrations ◽  
Target Attainment ◽  
Art Initiation ◽  
Tb Treatment ◽  
Before And After

Abstract Background Reduced ethambutol serum concentrations are commonly observed among TB patients co-infected with HIV and may lead to treatment failure. Objectives To perform a population pharmacokinetic study of ethambutol in HIV/TB patients, and to evaluate an intensified ethambutol weight-based dosing strategy to support pharmacokinetic target attainment. Methods We conducted a prospective study of ethambutol pharmacokinetics among HIV/TB patients administered first-line TB treatment in Botswana, with study visits before and after initiation of ART. Clinical and disease status markers, including HIV-associated systemic immune activation and gut dysfunction biomarkers, were evaluated as covariates of ethambutol pharmacokinetic parameters in non-linear mixed effects analysis. Monte Carlo simulations were performed to compare pharmacokinetic target attainment under standard and intensified weight-based ethambutol dosing strategies. Results We studied 40 HIV/TB patients prior to initiation of ART, of whom 24 returned for a second visit a median of 33 days following ART initiation. Ethambutol serum concentrations were best explained by a two-compartment model with first-order elimination, with a significant improvement in oral bioavailability following ART initiation. In Monte Carlo simulations, a supplementary ethambutol dose of 400 mg daily led to >2-fold improvements in pharmacokinetic target attainment probabilities in lung tissue, both before and after ART initiation. Conclusions Low serum ethambutol concentrations were commonly observed among HIV/TB patients in Botswana, and the oral bioavailability of ethambutol increased following ART initiation. Supplementary ethambutol dosing among HIV/TB patients may provide a strategy to optimize anti-TB treatment regimens in this high-risk population.

scholarly journals Use of Monte Carlo Simulations To Select Therapeutic Doses and Provisional Breakpoints of BAL9141

2004 ◽  
Vol 48 (5) ◽  
pp. 1713-1718 ◽  
Author(s):  
Johan W. Mouton ◽  
Anne Schmitt-Hoffmann ◽  
Stuart Shapiro ◽  
Norman Nashed ◽  
Nieko C. Punt
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Staphylococcus Epidermidis ◽  
Parameter Estimates ◽  
Dosing Regimen ◽  
Target Attainment ◽  
Methicillin Resistant ◽  
Dose Study ◽  
Time Periods ◽  
Therapeutic Doses

ABSTRACT BAL9141, a new antimicrobial agent belonging to the class of parenteral pyrrolidinone-3-ylidenemethyl cephalosporins, is active against most gram-positive microorganisms, including methicillin-resistant variants (methicillin-resistant Staphylococcus aureus [MRSA] and methicillin-resistant Staphylococcus epidermidis [MRSE]), as well as against penicillin-resistant pneumococci (PRP) and many gram-negative microorganisms. BAL9141 is administered as the prodrug BAL5788, which is rapidly converted to BAL9141 by plasma esterases. Pharmacokinetic (PK) data obtained in a previous multiple ascending dose study were used to fit a population PK model to using the NPEM2 program, yielding PK parameter estimates and its covariance matrix for BAL9141. These estimates and matrix were used to perform Monte Carlo simulations (MCSs) and obtain unbiased target attainment rates (TARs) for various time periods during which the concentration remains above the MIC (T >MIC). Assuming a T >MIC of 40%, TARs of 100% were reached with a dose of 500 mg/liter every 12 h for pathogens with MICs of 2 mg/liter and with a dose of 750 mg/liter every 12 h for pathogens with MICs of 4 mg/liter. Because MICs are ≤2 mg/liter for most strains of MRSA, MRSE, and PRP (with some strains showing an MIC of 4 mg/liter), a dosing regimen of 750 mg every 12 h is proposed for clinical studies. The corresponding provisional breakpoint is S (susceptible) ≤ 4 mg/liter.

Intravenous Vancomycin Pharmacokinetics in Automated Peritoneal Dialysis Patients

2001 ◽  
Vol 21 (4) ◽  
pp. 378-385 ◽  
Author(s):  
Harold J. Manley ◽  
George R. Bailie ◽  
Reginald F. Frye ◽  
M. Donald McGoldrick
Keyword(s):  
Peritoneal Dialysis ◽  
Filtration Rate ◽  
Inhibitory Concentration ◽  
Total Body Weight ◽  
Compartment Model ◽  
Automated Peritoneal Dialysis ◽  
Dialysis Patients ◽  
Once Daily ◽  
Blood Samples ◽  
Total Body

The pharmacokinetics of intravenous (IV) vancomycin was studied in automated peritoneal dialysis (APD) patients who received a single IV dose of vancomycin (15 mg/kg total body weight). Dialysate samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwells 4 and 5 (off-cycler), for a 24-hour period. Blood samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwell 5 (off-cycler) for a 24-hr period. Pharmacokinetics parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and vancomycin clearance (Cl) values were normalized to 1.73 m2. Ten patients [4 males, 6 females; 47.4 ± 9.9 years of age (mean ± SD)] who had received PD for a median 3.5 months (range 2 – 66 months) were studied. Dwell times were 2.3 ± 0.1 hours on cycler and 7.3 ± 0.1 hours off cycler. Vancomycin half-life was significantly different on-cycler than off-cycler (11.6 ± 5.2 hr vs 62.8 ± 33.0 hr; p < 0.001). Vancomycin total Cl (ClT) was 7.4 ± 2.0 mL/min. Renal Cl (ClR) and PD Cl (ClPD) accounted for 23.6% and 28.0% of ClT, respectively. ClR correlated with GFR (ClR = 0.90 GFR – 1.01; r2 = 0.79; p = 0.008). Mean vancomycin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (5 mg/mL) for the first cycler and the second ambulatory exchanges only. The results of this study suggest that, to provide adequate concentrations for susceptible organisms over a 24-hour period, current intermittent vancomycin dosing recommendations for PD-related peritonitis need to be changed to 35 mg/kg intraperitoneally on day 1, then 15 mg/kg IP thereafter ( i.e., once daily) in APD patients.

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