Population Pharmacokinetics and Pharmacodynamic Target Attainment of Ampicillin in Neonates with Hypoxemic-Ischemic Encephalopathy in the Setting of Controlled Hypothermia

2017 ◽  
Vol 37 (4) ◽  
pp. 456-463 ◽  
Author(s):  
Jeffrey J. Cies ◽  
Keri N. Fugarolas ◽  
Wayne S. Moore ◽  
Robert W. Mason ◽  
Ogechukwu R. Menkiti
Keyword(s):  
Population Pharmacokinetics ◽  
Target Attainment ◽  
Controlled Hypothermia ◽  
Ischemic Encephalopathy

scholarly journals Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

2020 ◽  
Vol 76 (7) ◽  
pp. 957-967
Author(s):  
Alan Abdulla ◽  
Omar Rogouti ◽  
Nicole G. M. Hunfeld ◽  
Henrik Endeman ◽  
Annemieke Dijkstra ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Target Attainment

Controlled hypothermia in complex therapy for hypoxic ischemic encephalopathy in infants with birth asphyxia

2020 ◽  
Vol 5_2020 ◽  
pp. 90-97
Author(s):  
Savelyeva G.М. Savelyeva ◽  
Shalina R.I. Shalina ◽  
Аnаnkina А.А. Аnаnkina ◽  
Kunyakh Zh.Yu Kunyakh ◽  
Sichinava L.G. Sichinava ◽  
...  
Keyword(s):  
Birth Asphyxia ◽  
Hypoxic Ischemic Encephalopathy ◽  
Complex Therapy ◽  
Controlled Hypothermia ◽  
Ischemic Encephalopathy

Population pharmacokinetics and target attainment analysis of moxifloxacin in patients with diabetic foot infections

2015 ◽  
Vol 55 (6) ◽  
pp. 639-646 ◽  
Author(s):  
Sebastian G. Wicha ◽  
Thomas Haak ◽  
Karl Zink ◽  
Frieder Kees ◽  
Charlotte Kloft ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Diabetic Foot ◽  
Target Attainment ◽  
Diabetic Foot Infections

Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Neonates on Extracorporeal Life Support

2017 ◽  
Vol 18 (10) ◽  
pp. 977-985 ◽  
Author(s):  
Jeffrey J. Cies ◽  
Wayne S. Moore ◽  
Kristen Nichols ◽  
Chad A. Knoderer ◽  
Dominick M. Carella ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Target Attainment

scholarly journals Population Pharmacokinetics and Target Attainment of Ertapenem in Plasma and Tissue Assessed via Microdialysis in Morbidly Obese Patients after Laparoscopic Visceral Surgery

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Mathias Wittau ◽  
Stephan Paschke ◽  
Max Kurlbaum ◽  
Jan Scheele ◽  
Neang S. Ly ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Peritoneal Fluid ◽  
Subcutaneous Tissue ◽  
Plasma Concentrations ◽  
Fat Free Mass ◽  
Morbidly Obese ◽  
Population Pharmacokinetic ◽  
Obese Patients ◽  
Target Attainment ◽  
Tissue Penetration

ABSTRACT Ertapenem provides broad-spectrum activity against many pathogens, and its use is relevant for the prophylaxis and treatment of infections in morbidly obese patients undergoing surgery. However, its pharmacokinetics and tissue penetration in these patients are not well defined. We assessed the population pharmacokinetics and target attainment for ertapenem in the plasma, subcutaneous tissue, and peritoneal fluid of morbidly obese patients. Six female patients (body mass index, 43.7 to 55.9 kg/m2) received 1,000 mg ertapenem as 15-min infusions at 0 and 26 h. On day 2, the unbound ertapenem concentrations in plasma, subcutaneous tissue, and peritoneal fluid were measured by microdialysis; total plasma concentrations were additionally quantified. The probability of attaining a target of an unbound ertapenem concentration above the MIC for at least 40% of the dosing interval was predicted via Monte Carlo simulations. The population pharmacokinetic model contained two disposition compartments and simultaneously described all concentrations. For unbound ertapenem, total clearance was 12.3 liters/h (coefficient of variation, 21.6% for between-patient variability) and the volume of distribution at steady state was 57.8 liters in patients with a 53-kg fat-free mass. The area under the concentration-time curve (AUC) for ertapenem was 49% lower in subcutaneous tissue and 25% lower in peritoneal fluid than the unbound AUC in plasma. Tissue penetration was rapid (equilibration half-life, <15 min) and was variable in subcutaneous tissue. Short-term ertapenem infusions (1,000 mg every 24 h) achieved robust (>90%) target attainment probabilities for MICs of up to 1 mg/liter in plasma, 0.25 to 0.5 mg/liter in subcutaneous tissue, and 0.5 mg/liter in peritoneal fluid. Ertapenem presents an attractive choice for many pathogens relevant to morbidly obese patients undergoing surgery. (This study has been registered at ClinicalTrials.gov under identifier NCT01407965.)

scholarly journals Tedizolid Population Pharmacokinetics, Exposure Response, and Target Attainment

2014 ◽  
Vol 58 (11) ◽  
pp. 6462-6470 ◽  
Author(s):  
S. Flanagan ◽  
J. Passarell ◽  
Q. Lu ◽  
J. Fiedler-Kelly ◽  
E. Ludwig ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Coefficient Of Variation ◽  
Safety Data ◽  
Absolute Bioavailability ◽  
Optimum Dose ◽  
Target Attainment ◽  
Time Curve ◽  
Unbound Fraction ◽  
Once Daily ◽  
Content Type

ABSTRACTTedizolid phosphate is a novel antibacterial prodrug that is rapidly and extensively converted to its active moiety, tedizolid. We developed a population pharmacokinetics (PK) model for tedizolid using pooled data from seven densely and sparsely sampled clinical trials evaluating oral and intravenous tedizolid. Model-derived exposure estimates were evaluated for relationships to select efficacy and safety outcomes. A two-compartment model with sigmoidal absorption, absolute bioavailability, and linear elimination described the PK data well. Variability was small (clearance, 31% coefficient of variation; volume, 13.4% coefficient of variation), and absolute bioavailability was high (86%). No clinically significant covariate effects on tedizolid PK were found. Based on phase 3 data evaluating 200-mg once-daily tedizolid for acute bacterial skin and skin structure infections (ABSSSI), no relationships were seen between various efficacy outcomes and estimated tedizolid exposure; the estimated exposure range (free-drug area under the concentration-time curve over 24 h at steady state [AUCss(0–24)], 7 to 50 μg · h/ml) in these patients was modest. Safety data modeling, using once-daily doses of up to 400 mg, showed a small increase in the probability of an adverse event with increasing model-estimated tedizolid exposure; no such relationship was observed when specifically evaluating the 200-mg dose. There were no trends in neutrophil or platelet counts with increasing tedizolid exposure. Target attainment simulations for 200-mg tedizolid indicated a 98.31% probability of attaining the target measure (AUC for the free, unbound fraction of a drug [fAUC]/MIC = 3) against aStaphylococcus aureusstrain for which the MIC was ≤0.5 μg/ml. These findings support 200-mg tedizolid once daily as the optimum dose for treatment of ABSSSI.

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