Pharmacokinetics and Pharmacodynamics of Cefepime in Patients with Various Degrees of Renal Function

ABSTRACT This study evaluated the pharmacokinetics of cefepime in 36 patients with different levels of renal function. Pharmacokinetic and pharmacodynamic parameters were calculated using samples obtained at steady state. Patients with creatinine clearance (CLCR) of >100 ml/min had more rapid clearance (CL) and a lower minimum concentration in serum (C min). C min in this group was found to be 3.3 ± 3.6 mg/liter (mean and standard deviation), compared to 19.5 ± 21.5 mg/liter in patients with a CLCR of between 60 and 100 ml/min (P = 0.025) and 14.0 ± 11.5 mg/liter in patients with a CLCR of <60 ml/min (P = 0.009). Patient data were also analyzed by the nonparametric expectation maximization method and Bayesian forecasting. The median volume of distribution in the central compartment was 27.08 liters. CL and CLCR were highly correlated (P = 0.00033) according to the equation CL= 0.324 liters/h + (0.0551 × CLCR). The median rate constants from the central compartment to the peripheral compartment and from the peripheral compartment to the central compartment were 12.58 and 41.09 h−1, respectively. The time-concentration profiles for 1,000 patients (CLCRs, 120, 60, and 30 ml/min) each receiving various dosing regimens were simulated by using Monte Carlo simulations. Standard dosing resulted in a C min that was greater than or equal to the MIC in more than 80% of the simulated profiles with MICs ≤2 mg/liter. Current dosing recommendations may be suboptimal for monotherapy of infections due to less susceptible pathogens (e.g., those for which MICs are ≥4 mg/liter), particularly when CLCR exceeds 120 ml/min.

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Population Pharmacokinetic Model for Vancomycin Used in Open Heart Surgery: Model-Based Evaluation of Standard Dosing Regimens

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00088-18 ◽

2018 ◽

Vol 62 (7) ◽

Cited By ~ 1

Author(s):

Saeed A. Alqahtani ◽

Abdullah S. Alsultan ◽

Hussain M. Alqattan ◽

Ahmed Eldemerdash ◽

Turki B. Albacker

Keyword(s):

Heart Surgery ◽

Open Heart Surgery ◽

Central Compartment ◽

Volume Of Distribution ◽

Peripheral Compartment ◽

Population Pharmacokinetic ◽

Albumin Concentration ◽

Open Heart ◽

Blood Samples ◽

Dosing Regimens

ABSTRACTThe purpose of this study was to investigate the population pharmacokinetics of vancomycin in patients undergoing open heart surgery. In this observational pharmacokinetic study, multiple blood samples were drawn over a 48-h period of intravenous vancomycin in patients who were undergoing open heart surgery. Blood samples were analyzed using an Architect i4000SR immunoassay analyzer. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 168 blood samples were analyzed from 28 patients. The pharmacokinetics of vancomycin are best described by a two-compartment model with between-subject variability in clearance (CL), the volume of distribution of the central compartment (V1), and volume of distribution of the peripheral compartment (V2). The CL and theV1of vancomycin were related to creatinine CL (CLCR), body weight, and albumin concentration. Dosing simulations showed that standard dosing regimens of 1 and 1.5 g failed to achieve the PK-PD target of AUC0–24/MIC > 400 for an MIC of 1 mg/liter, while high weight-based dosing regimens were able to achieve the PK-PD target. In summary, the administration of standard doses of 1 and 1.5 g of vancomycin two times daily provided inadequate antibiotic prophylaxis in patients undergoing open heart surgery. The same findings were obtained when 15- and 20-mg/kg doses of vancomycin were administered. Achieving the PK-PD target required higher doses (25 and 30 mg/kg) of vancomycin.

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Pharmacokinetics of Telavancin in Adult Patients with Cystic Fibrosis during Acute Pulmonary Exacerbation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01914-19 ◽

2019 ◽

Vol 64 (1) ◽

Author(s):

James M. Kidd ◽

Colleen M. Sakon ◽

Louise-Marie Oleksiuk ◽

Jeffrey J. Cies ◽

Rebecca S. Pettit ◽

...

Keyword(s):

Cystic Fibrosis ◽

Body Weight ◽

Total Body Weight ◽

Central Compartment ◽

Volume Of Distribution ◽

Peripheral Compartment ◽

Population Pharmacokinetic ◽

Minimal Risk ◽

Content Type ◽

Total Body

ABSTRACT Adults with cystic fibrosis (CF) frequently harbor Staphylococcus aureus, which is increasingly antibiotic resistant. Telavancin is a once-daily rapidly bactericidal antibiotic active against methicillin-, linezolid-, and ceftaroline-resistant S. aureus. Because CF patients experience alterations in pharmacokinetics, the optimal dose of telavancin in this population is unknown. Adult CF patients (n = 18) admitted for exacerbations received 3 doses of telavancin 7.5 mg/kg of body weight (first 6 patients) or 10 mg/kg (final 12 patients) every 24 h (q24h). Population pharmacokinetic models with and without covariates were fitted using the nonparametric adaptive grid algorithm in Pmetrics. The final model was used to perform 5,000-patient Monte Carlo simulations for multiple telavancin doses. The best fit was a 2-compartment model describing the volume of distribution of the central compartment (Vc) as a multiple of total body weight (TBW) and the volume of distribution of the central compartment scaled to total body weight (Vθ) normalized by the median observed value (Vc = Vθ × TBW/52.1) and total body clearance (CL) as a linear function of creatinine clearance (CRCL) (CL = CLNR + CLθ × CRCL), where CLNR represents nonrenal clearance and CLθ represents the slope term on CRCL to estimate renal clearance. The mean population parameters were as follows: Vθ, 4.92 ± 0.76 liters · kg−1; CLNR, 0.59 ± 0.30 liters · h−1; CLθ, 5.97 × 10−3 ± 1.24 × 10−3; Vp (volume of the peripheral compartment), 3.77 ± 1.41 liters; Q (intercompartmental clearance), 4.08 ± 2.17 liters · h−1. The free area under the concentration-time curve (fAUC) values for 7.5 and 10 mg/kg were 30 ± 4.6 and 52 ± 12 mg · h/liter, respectively. Doses of 7.5 mg/kg and 10 mg/kg achieved 76.5% and 100% probability of target attainment (PTA) at a fAUC/MIC threshold of >215, respectively, for MIC of ≤0.12 mg/liter. The probabilities of reaching the acute kidney injury (AKI) threshold AUC (763 mg · h · liter−1) for these doses were 0% and 0.96%, respectively. No serious adverse events occurred. Telavancin 10 mg/kg yielded optimal PTA and minimal risk of AKI, suggesting that this FDA-approved dose is appropriate to treat acute pulmonary exacerbations in CF adults. (The clinical trial discussed in this study has been registered at ClinicalTrials.gov under identifier NCT03172793.)

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Population-based meta-analysis of chloroquine: informing chloroquine pharmacokinetics in COVID-19 patients

European Journal of Clinical Pharmacology ◽

10.1007/s00228-020-03032-6 ◽

2020 ◽

Author(s):

Xueting Yao ◽

Xiaoyu Yan ◽

Xiaohan Wang ◽

Ting Cai ◽

Shun Zhang ◽

...

Keyword(s):

Meta Analysis ◽

Safety Margin ◽

Volume Of Distribution ◽

Population Based ◽

Ethical Review ◽

Peripheral Compartment ◽

Dosing Regimen ◽

First Order ◽

Population Pk ◽

Dosing Regimens

Abstract Aims Chloroquine (CQ) has been repurposed to treat coronavirus disease 2019 (COVID-19). Understanding the pharmacokinetics (PK) in COVID-19 patients is essential to study its exposure–efficacy/safety relationship and provide a basis for a possible dosing regimen optimization. Subject and methods In this study, we used a population-based meta-analysis approach to develop a population PK model to characterize the CQ PK in COVID-19 patients. An open-label, single-center study (ethical review approval number: PJ-NBEY-KY-2020-063-01) was conducted to assess the safety, efficacy, and pharmacokinetics of CQ in patients with COVID-19. The sparse PK data from 50 COVID-19 patients, receiving 500 mg CQ phosphate twice daily for 7 days, were combined with additional CQ PK data from 18 publications. Results A two-compartment model with first-order oral absorption and first-order elimination and an absorption lag best described the data. Absorption rate (ka) was estimated to be 0.559 h−1, and a lag time of absorption (ALAG) was estimated to be 0.149 h. Apparent clearance (CL/F) and apparent central volume of distribution (V2/F) was 33.3 l/h and 3630 l. Apparent distribution clearance (Q/F) and volume of distribution of peripheral compartment (Q3/F) were 58.7 l/h and 5120 l. The simulated CQ concentration under five dosing regimens of CQ phosphate were within the safety margin (400 ng/ml). Conclusion Model-based simulation using PK parameters from the COVID-19 patients shows that the concentrations under the currently recommended dosing regimen are below the safety margin for side-effects, which suggests that these dosing regimens are generally safe. The derived population PK model should allow for the assessment of pharmacokinetics–pharmacodynamics (PK-PD) relationships for CQ when given alone or in combination with other agents to treat COVID-19.

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Population pharmacokinetics (PPK) of eribulin mesylate in patients with locally advanced or metastatic breast cancer (MBC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.2524 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 2524-2524 ◽

Cited By ~ 2

Author(s):

M. Jansen ◽

M. Vernaz-Gris ◽

C. DesJardins ◽

N. Wong ◽

M. Campone ◽

...

Keyword(s):

Renal Function ◽

Locally Advanced ◽

Metastatic Breast ◽

Compartment Model ◽

Central Compartment ◽

Volume Of Distribution ◽

Eribulin Mesylate ◽

Minor Fraction ◽

Three Compartment Model ◽

A Minor

2524 Background: Eribulin mesylate (E7389) is a non-taxane microtubule dynamics inhibitor with a novel mechanism of action. A study was conducted to evaluate efficacy, safety and pharmacokinetics of eribulin at a dose of 1.4 mg/m2 for locally advanced or MBC in patients previously treated with an anthracycline, a taxane, and capecitabine. Methods: Eribulin was administered intravenously over 2–5 minutes at a dose of 1.4 mg/m2 on days 1 and 8 of a 21- day cycle to 291 patients. Four plasma samples were collected between 5 min and 120 hours after the first dose. Plasma eribulin concentrations were determined by LC/MS/MS. A total of 774 samples, from 209 patients with complete dose and sampling information were included in the PPK analysis, which was conducted using nonlinear mixed effects modeling (NONMEM). Results: Eribulin PKs were best described by a three-compartment model, with elimination from the central compartment. Distribution was rapid and elimination slow. For a typical patient with AST<ULN and CLCR=101mL/min (Cockroft-Gault), clearance (CL) was 2.98 L/h and central volume of distribution 3.72 L (V1). Volumes and inter-compartmental clearances for the two peripheral compartments were 3.60 L (V2), 126 L (V3), 2.7 L/h (Q2) and 5.6 L/h (Q3). Inter-patient variability on CL was 57%, and ranged from 26- 98% for other parameters. Residual error was 21% (proportional). CL was on average 38% lower in patients with AST>ULN and positively correlated with renal function. The covariate effects only explained a minor fraction of inter-patient variability in this single study dataset. Conclusions: Eribulin PKs were described by a three-compartment model with rapid distribution and slow elimination. Appreciable interpatient PK variability exists, a minor fraction of which was explained by measures of liver and renal function. [Table: see text]

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Pharmacokinetic Profile of Kaurenoic Acid after Oral Administration of Araliae Continentalis Radix Extract Powder to Humans

Pharmaceutics ◽

10.3390/pharmaceutics10040253 ◽

2018 ◽

Vol 10 (4) ◽

pp. 253

Author(s):

Eun-Jeong Choi ◽

Go-Wun Choi ◽

Seung-Jeong Yang ◽

Yong-Bok Lee ◽

Hea-Young Cho

Keyword(s):

Plasma Concentrations ◽

Compartment Model ◽

Central Compartment ◽

Volume Of Distribution ◽

Efflux Transporters ◽

Peripheral Compartment ◽

Simple Liquid ◽

Usual Dose ◽

Kaurenoic Acid

The objective of this study was to characterize pharmacokinetics (PKs) of kaurenoic acid (KAU) after administration of the clinical usual dose of Araliae Continentalis Radix extract powder to Korean subjects for the first time and evaluate the mechanism of its absorption in vitro. A simple, sensitive, and selective analytical method was developed for the detection of KAU in human plasma. Concentrations of KAU were quantified by ultra-performance liquid chromatography tandem mass spectrometry after simple liquid–liquid extraction. This pharmacokinetic model of KAU was best described by a two-compartment model with first-order absorption. To identify efflux transporters involved in the absorption of KAU, a Caco-2 monolayer model was used. Estimated PK parameters were: systemic clearance, 23.89 L/h; inter-compartmental clearance, 15.55 L/h; rate constant for absorption, 1.72 h−1; volume of distribution of the central compartment, 24.44 L; and volume of distribution of the peripheral compartment, 64.05 L. Results from Caco-2 bidirectional transport study suggested that KAU was a potential substrate of efflux transporters. In summary, PKs of KAU were successfully characterized after administration of a usual dose of Araliae continentalis Radix extract powder in human with the newly developed bioanalytical method and the mechanism of absorption of KAU was identified clearly.

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Population Pharmacokinetics and Safety of Piperacillin-Tazobactam Extended Infusions in Infants and Children

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01260-19 ◽

2019 ◽

Vol 63 (11) ◽

Cited By ~ 1

Author(s):

Céline Thibault ◽

Jean Lavigne ◽

Catherine Litalien ◽

Nastya Kassir ◽

Yves Théorêt ◽

...

Keyword(s):

Adverse Event ◽

Standard Of Care ◽

Compartment Model ◽

Central Compartment ◽

Volume Of Distribution ◽

Content Type ◽

Final Population ◽

Optimal Dosing ◽

Population Pk ◽

Dosing Regimens

ABSTRACT Piperacillin-tazobactam (TZP) is frequently used to treat severe hospital-acquired infections in children. We performed a single-center, pharmacokinetic (PK) trial of TZP in children ranging in age from 2 months to 6 years from various clinical subpopulations. Children who were on TZP per the standard of care were prospectively included and assigned to receive a dose of 80 mg/kg of body weight every 6 h infused over 2 h (ages 2 to 5 months) or a dose of 90 mg/kg every 8 h infused over 4 h (ages 6 months to 6 years). Separate population PK models were developed for piperacillin and tazobactam using nonlinear mixed-effects modeling. Optimal dosing was judged based on the ability to maintain free piperacillin concentrations above the piperacillin MIC for enterobacteria and Pseudomonas aeruginosa for ≥50% of the dosing interval. Any untoward event occurring during treatment was collected as an adverse event. A total of 79 children contributed 174 PK samples. The median (range) age and weight were 1.7 years (2 months to 6 years) and 11.4 kg (3.8 to 27.6 kg), respectively. A 2-compartment model with first-order elimination best described the piperacillin and tazobactam data. Both final population PK models included weight and concomitant furosemide administration on clearance and weight on the volume of distribution of the central compartment. The optimal dosing regimens in children with normal renal function, based on the piperacillin component, were 75 mg/kg/dose every 4 h infused over 0.5 h in infants ages 2 to ≤6 months and 130 mg/kg/dose every 8 h infused over 4 h in children ages >6 months to 6 years against bacteria with MICs up to 16 mg/liter. A total of 44 children (49%) had ≥1 adverse event, with 3 of these (site infiltrations) considered definitely associated with the extended infusions.

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Pharmacokinetics of Anidulafungin in Critically Ill Intensive Care Unit Patients with Suspected or Proven Invasive Fungal Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01894-16 ◽

2016 ◽

Vol 61 (2) ◽

Cited By ~ 15

Author(s):

R. J. M. Brüggemann ◽

V. Middel-Baars ◽

D. W. de Lange ◽

A. Colbers ◽

A. R. J. Girbes ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Critically Ill ◽

Fungal Infections ◽

Geometric Mean ◽

Volume Of Distribution ◽

Time Curve ◽

Icu Patients ◽

Minimum Concentration ◽

Median Volume

ABSTRACT Echinocandins, such as anidulafungin, are the first-line treatment for candidemia or invasive candidiasis in critically ill patients. There are conflicting data on the pharmacokinetic properties of anidulafungin in intensive care unit (ICU) patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included in the present study. Patients were considered evaluable if a pharmacokinetic curve for day 3 could be completed. Twenty-three of 36 patients (7 female and 16 male) were evaluable. The median (range) age and body weight were 66 (28 to 88) years and 76 (50 to 115) kg, respectively. Pharmacokinetic sampling on day 3 (n = 23) resulted in a median anidulafungin area under the concentration-time curve from 0 to 24 h (AUC0–24) of 72.1 (interquartile range [IQR], 61.3 to 94.0) mg · h · liter−1, a median daily trough concentration (C 24) of 2.2 (IQR, 1.9 to 2.9) mg/liter, a median maximum concentration of drug in serum (C max) of 5.3 (IQR, 4.1 to 6.0) mg/liter, a median volume of distribution (V) of 46.0 (IQR, 32.2 to 60.2) liters, and a median clearance (CL) of 1.4 (IQR, 1.1 to 1.6) liters · h−1. Pharmacokinetic sampling on day 7 (n = 13) resulted in a median AUC0–24 of 82.7 (IQR, 73.0 to 129.5) mg · h · liter−1, a median minimum concentration of drug in serum (C min) of 2.8 (IQR, 2.2 to 4.2) mg/liter, a median C max of 5.9 (IQR, 4.6 to 8.0) mg/liter, a median V of 39.7 (IQR, 32.2 to 54.4) liters, and a median CL of 1.2 (IQR, 0.8 to 1.4) liters · h−1. The geometric mean ratio for the AUCday7/AUCday3 term was 1.13 (90% confidence interval [CI], 1.03 to 1.25). The exposure in the ICU patient population was in accordance with previous reports on anidulafungin pharmacokinetics in ICU patients but was lower than that for healthy volunteers or other patient populations. Larger cohorts of patients or pooled data analyses are necessary to retrieve relevant covariates. (This study has been registered at ClinicalTrials.gov under identifier NCT01438216.)

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Pharmacometrics-Based Dose Selection of Levofloxacin as a Treatment for Postexposure Inhalational Anthrax in Children

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00667-09 ◽

2009 ◽

Vol 54 (1) ◽

pp. 375-379 ◽

Cited By ~ 30

Author(s):

Fang Li ◽

Partha Nandy ◽

Shuchean Chien ◽

Gary J. Noel ◽

Christoffer W. Tornoe

Keyword(s):

Body Weight ◽

Steady State ◽

Pediatric Patients ◽

Volume Of Distribution ◽

Dose Selection ◽

Time Curve ◽

Minimum Concentration ◽

Pediatric Dose ◽

Adult Dose ◽

Dosing Regimens

ABSTRACT Levofloxacin was recently (May 2008) approved by the U.S. Food and Drug Administration as a treatment for children following inhalational exposure to anthrax. Given that no clinical trials to assess the efficacy of a chosen dose was conducted, the basis for the dose recommendation was based upon pharmacometric analyses. The objective of this paper is to describe the basis of the chosen pediatric dose recommended for the label. Pharmacokinetic (PK) data from 90 pediatric patients receiving 7 mg/kg of body weight levofloxacin and two studies of 47 healthy adults receiving 500 and 750 mg/kg levofloxacin were used for the pharmacometric analyses. Body weight was found to be a significant covariate for levofloxacin clearance and the volume of distribution. Consistently with developmental physiology, clearance also was found to be reduced in pediatric patients under 2 years of age due to immature renal function. Different dosing regimens were simulated to match adult exposure (area under the concentration-time curve from 0 to 24 h at steady state, maximum concentration of drug in serum at steady state, and minimum concentration of drug in serum at steady state) following the approved adult dose of 500 mg once a day. The recommended dose of 8 mg/kg twice a day was found to match the exposure of the dose approved for adults in a manner that permitted confidence that this dose in children would achieve efficacy comparable to that of adults.

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Pharmacokinetics of Intravenous and Oral Linezolid in Adults with Cystic Fibrosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01797-10 ◽

2011 ◽

Vol 55 (7) ◽

pp. 3393-3398 ◽

Cited By ~ 33

Author(s):

Rebecca A. Keel ◽

Andre Schaeftlein ◽

Charlotte Kloft ◽

J. Samuel Pope ◽

R. Frederic Knauft ◽

...

Keyword(s):

Cystic Fibrosis ◽

Compartment Model ◽

Central Compartment ◽

Time Dependent ◽

Peripheral Compartment ◽

Population Pharmacokinetic ◽

Parameter Estimates ◽

Content Type ◽

Mixed Effects Modeling ◽

Dosing Regimens

ABSTRACTLinezolid is a treatment option for methicillin-resistantStaphylococcus aureus(MRSA) infections in cystic fibrosis (CF) patients. Little is known, however, about its pharmacokinetics in this population. Eight adults with CF were randomized to receive intravenous (i.v.) and oral linezolid at 600 mg twice daily for 9 doses in a crossover design with a 9-day washout. Plasma samples were collected after the first and ninth doses of each phase. Population pharmacokinetic analyses were performed by nonlinear mixed-effects modeling using a previously described 2-compartment model with time-dependent clearance inhibition. Monte Carlo simulation was performed to assess the activities of the linezolid dosing regimens against 42 contemporary MRSA isolates recovered from CF patients. The following pharmacokinetic parameter estimates were observed for the population: absorption rate constant, 1.91 h−1; clearance, 9.54 liters/h; volume of central compartment, 26.8 liters; volume of peripheral compartment, 17.3 liters; and intercompartmental clearance, 104 liters/h. Linezolid demonstrated nonlinear clearance after 9 doses, which was reduced by a mean of 38.9% (range, 28.8 to 59.9%). Mean bioavailability was 85% (range, 47 to 131%). At steady state, 600 mg given twice daily produced 93.0% and 87.2% probabilities of obtaining the target pharmacodynamic exposure against the MRSA isolates for the i.v. and oral formulations, respectively. Thrice-daily dosing increased the probabilities to 97.0% and 95.6%, respectively. Linezolid pharmacokinetics in these adults with CF were well described by a 2-compartment model with time-dependent clearance inhibition. Standard i.v. and oral dosing regimens should be sufficient to reliably attain pharmacodynamic targets against most MRSA isolates; however, more frequent dosing may be required for isolates with MICs of ≥2 μg/ml.

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Pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01657-16 ◽

2016 ◽

pp. AAC.01657-16 ◽

Cited By ~ 2

Author(s):

Danny Tsai ◽

Penelope Stewart ◽

Rajendra Goud ◽

Stephen Gourley ◽

Saliya Hewagama ◽

...

Keyword(s):

Severe Sepsis ◽

Critically Ill ◽

Total Body Weight ◽

Compartment Model ◽

Central Compartment ◽

Volume Of Distribution ◽

Peripheral Compartment ◽

Population Pharmacokinetic ◽

Pharmacokinetic Data ◽

Population Pharmacokinetic Study

Objectives: There are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis.Methods: A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modelling was conducted using Pmetrics®.Results: Nine patients were recruited and a two compartment model adequately described the data. Piperacillin clearance (CL), volume of distribution of the central compartment (Vc), distribution rate constant from central to peripheral compartment and from peripheral to central compartment were 5.6 ± 3.2 L/h, 14.5 ± 6.6 L, 1.5 ± 0.4 h-1and 1.8 ± 0.9 h-1respectively, where CL and Vcwere found to be described by creatinine clearance (CrCL) and total body weight respectively.Conclusion: In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CrCL were found to be the most important determinant of piperacillin pharmacokinetics.

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