Isoniazid Population Pharmacokinetics and Dose Recommendation for Korean Patients with Tuberculosis Based on Target Attainment Analysis

Author(s):  
Yong‐Soon Cho ◽  
Tae Won Jang ◽  
Hyo‐Jung Kim ◽  
Jee Youn Oh ◽  
Hyun‐Kyung Lee ◽  
...  

2020 ◽  
Vol 76 (7) ◽  
pp. 957-967
Author(s):  
Alan Abdulla ◽  
Omar Rogouti ◽  
Nicole G. M. Hunfeld ◽  
Henrik Endeman ◽  
Annemieke Dijkstra ◽  
...  


2015 ◽  
Vol 55 (6) ◽  
pp. 639-646 ◽  
Author(s):  
Sebastian G. Wicha ◽  
Thomas Haak ◽  
Karl Zink ◽  
Frieder Kees ◽  
Charlotte Kloft ◽  
...  


2017 ◽  
Vol 18 (10) ◽  
pp. 977-985 ◽  
Author(s):  
Jeffrey J. Cies ◽  
Wayne S. Moore ◽  
Kristen Nichols ◽  
Chad A. Knoderer ◽  
Dominick M. Carella ◽  
...  


2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Mathias Wittau ◽  
Stephan Paschke ◽  
Max Kurlbaum ◽  
Jan Scheele ◽  
Neang S. Ly ◽  
...  

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.)



2014 ◽  
Vol 58 (11) ◽  
pp. 6462-6470 ◽  
Author(s):  
S. Flanagan ◽  
J. Passarell ◽  
Q. Lu ◽  
J. Fiedler-Kelly ◽  
E. Ludwig ◽  
...  

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.



2022 ◽  
Vol Volume 15 ◽  
pp. 53-62
Author(s):  
Matthias Gijsen ◽  
Omar Elkayal ◽  
Pieter Annaert ◽  
Ruth Van Daele ◽  
Philippe Meersseman ◽  
...  


Author(s):  
Kyung-Sang Yu ◽  
Kyun-Seop Bae ◽  
Ju-Yeun Lee ◽  
Joo-Youn Cho ◽  
In-Jin Jang ◽  
...  


2002 ◽  
Vol 27 (6) ◽  
pp. 419-425 ◽  
Author(s):  
H.-M. Park ◽  
S.-S. Kang ◽  
Y.-B. Lee ◽  
D.-J. Shin ◽  
O.-N. Kim ◽  
...  


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