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Antibiotics
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Clinical Pharmacokinetics of Antibiotics
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Clinical Pharmacokinetics of Antibiotics

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics of Drugs".

Deadline for manuscript submissions: closed (20 March 2023) | Viewed by 6208

Special Issue Editors

Dr. Nusrat Shafiq

E-Mail Website
Guest Editor
Postgraduate Institute of Medical Education & Research, Chandigarh, India
Interests: pharmacokinetics; clinical pharmacokinetics; pharmacodynamics; bioavailability; pharmaceutical development; pharmacokinetic modeling; clinical studies; clinical trials of pharmaceuticals; medical pharmacology; pharmacoepidemiology
Dr. Ashish K Kakkar

E-Mail Website
Guest Editor
Clinical Pharmacology Unit, Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Interests: antimicrobial use; pharmacokinetics; pharmacology; antimicrobial therapy

Special Issue Information

Dear Colleagues,

The determination of an appropriate dosing schedule of therapeutic agents is key to optimized treatment outcomes. Despite this understanding, dosing regimens guided by population pharmacokinetics, PK-PD or physiologically guided pharmacokinetic models are not routine. Understandably, these studies are difficult to carry out, particularly in special cohorts such as critically ill patients, paediatrics, pregnant women, those with renal and/or hepatic impairment, critically ill, obese or malnourished, to name a few. Dosing for infections in sanctuary sites such as the central nervous system or bone is yet another relatively less explored area.  Dose optimization is an exercise which starts with the preclinical development of a new chemical/biologic entity and goes on for the entire life cycle of a therapeutic or prophylactic agent. We have some remarkable examples from the field of infection where the dosing paradigm has shifted quite significantly based on clinical pharmacokinetic studies—aminoglycoside dosing being a case in point.  With progress made in analytics and modelling, various approaches can be used to address the dose-related query at hand. In the current issue of antibiotics, we hope to bring forth articles on the theme of clinical pharmacokinetics in order to bring this important issue into the fore. We would like to ask you to kindly submit articles which centre around the theme of clinical pharmacokinetics, particularly for the purpose of dose optimization, to make the dedicated issue a captivating and invigorating read for the scientific community in the field of infections.

Dr. Nusrat Shafiq
Dr. Ashish K Kakkar
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

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Research

10 pages, 579 KiB  
Article
Linezolid Pharmacokinetics and Its Association with Adverse Drug Reactions in Patients with Drug-Resistant Pulmonary Tuberculosis
by Chandrasekaran Padmapriyadarsini, Rajesh Solanki, S. M. Jeyakumar, Anuj Bhatnagar, M. Muthuvijaylaksmi, Bharathi Jeyadeepa, Devarajulu Reddy, Prashanth Shah, Rathinam Sridhar, Vikram Vohra and Namrata Kaur Bhui
Antibiotics 2023, 12(4), 714; https://doi.org/10.3390/antibiotics12040714 - 6 Apr 2023
Cited by 6 | Viewed by 2235
Abstract
We evaluated the relationship between the pharmacokinetic parameters of linezolid (LZD) and development of adverse drug reactions (ADRs) in patients with pulmonary drug-resistant tuberculosis. A prospective cohort of adults with pulmonary multidrug-resistant tuberculosis with additional resistance to fluoroquinolone (MDR-TBFQ+) received treatment [...] Read more.
We evaluated the relationship between the pharmacokinetic parameters of linezolid (LZD) and development of adverse drug reactions (ADRs) in patients with pulmonary drug-resistant tuberculosis. A prospective cohort of adults with pulmonary multidrug-resistant tuberculosis with additional resistance to fluoroquinolone (MDR-TBFQ+) received treatment with bedaquiline, delamanid, clofazimine, and LZD. Blood samples were collected during weeks 8 and 16 at eight time points over 24 h. The pharmacokinetic parameters of LZD were measured using high-performance liquid chromatography and associated with ADRs. Of the 165 MDR-TBFQ+ patients on treatment, 78 patients developed LZD-associated anemia and 69 developed peripheral neuropathy. Twenty-three patients underwent intense pharmacokinetic testing. Plasma median trough concentration was 2.08 µg/mL and 3.41 µg/mL, (normal <2 µg/mL) and AUC0-24 was 184.5 µg/h/mL and 240.5 µg/h/mL at weeks 8 and 16, respectively, showing a linear relationship between duration of intake and plasma levels. Nineteen patients showed LZD-associated ADRs-nine at week 8, twelve at week 16, and two at both weeks 8 and 16. Thirteen of the nineteen had high plasma trough and peak concentrations of LZD. A strong association between LZD-associated ADRs and plasma LZD levels was noted. Trough concentration alone or combinations of trough with peak levels are potential targets for therapeutic drug monitoring. Full article
(This article belongs to the Special Issue Clinical Pharmacokinetics of Antibiotics)
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12 pages, 1620 KiB  
Article
Physiologically-Based Pharmacokinetic Modelling to Predict the Pharmacokinetics and Pharmacodynamics of Linezolid in Adults and Children with Tuberculous Meningitis
by Carlijn H. C. Litjens, Laurens F. M. Verscheijden, Elin M. Svensson, Petra H. H. van den Broek, Hedwig van Hove, Jan B. Koenderink, Frans G. M. Russel, Rob E. Aarnoutse and Lindsey H. M. te Brake
Antibiotics 2023, 12(4), 702; https://doi.org/10.3390/antibiotics12040702 - 3 Apr 2023
Cited by 1 | Viewed by 2046
Abstract
Linezolid is used off-label for treatment of central nervous system infections. However, its pharmacokinetics and target attainment in cranial cerebrospinal fluid (CSF) in tuberculous meningitis patients is unknown. This study aimed to predict linezolid cranial CSF concentrations and assess attainment of pharmacodynamic (PD) [...] Read more.
Linezolid is used off-label for treatment of central nervous system infections. However, its pharmacokinetics and target attainment in cranial cerebrospinal fluid (CSF) in tuberculous meningitis patients is unknown. This study aimed to predict linezolid cranial CSF concentrations and assess attainment of pharmacodynamic (PD) thresholds (AUC:MIC of >119) in plasma and cranial CSF of adults and children with tuberculous meningitis. A physiologically based pharmacokinetic (PBPK) model was developed to predict linezolid cranial CSF profiles based on reported plasma concentrations. Simulated steady-state PK curves in plasma and cranial CSF after linezolid doses of 300 mg BID, 600 mg BID, and 1200 mg QD in adults resulted in geometric mean AUC:MIC ratios in plasma of 118, 281, and 262 and mean cranial CSF AUC:MIC ratios of 74, 181, and 166, respectively. In children using ~10 mg/kg BID linezolid, AUC:MIC values at steady-state in plasma and cranial CSF were 202 and 135, respectively. Our model predicts that 1200 mg per day in adults, either 600 mg BID or 1200 mg QD, results in reasonable (87%) target attainment in cranial CSF. Target attainment in our simulated paediatric population was moderate (56% in cranial CSF). Our PBPK model can support linezolid dose optimization efforts by simulating target attainment close to the site of TBM disease. Full article
(This article belongs to the Special Issue Clinical Pharmacokinetics of Antibiotics)
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12 pages, 2525 KiB  
Article
Population Pharmacokinetics of Prophylactic Cefazolin in Cardiac Surgery with Standard and Minimally Invasive Extracorporeal Circulation
by Petr Šantavý, Martin Šíma, Ondřej Zuščich, Vendula Kubíčková, Danica Michaličková, Ondřej Slanař and Karel Urbánek
Antibiotics 2022, 11(11), 1582; https://doi.org/10.3390/antibiotics11111582 - 9 Nov 2022
Cited by 2 | Viewed by 1538
Abstract
The objectives of this study were to develop a population pharmacokinetic model of prophylactically administered cefazolin in patients undergoing cardiac surgery with and without the use of the cardiopulmonary bypass of both existing types—standard (ECC) and minimallyu invasive extracorporeal circulation (MiECC)—and to propose [...] Read more.
The objectives of this study were to develop a population pharmacokinetic model of prophylactically administered cefazolin in patients undergoing cardiac surgery with and without the use of the cardiopulmonary bypass of both existing types—standard (ECC) and minimallyu invasive extracorporeal circulation (MiECC)—and to propose cefazoline dosing optimization based on this model. A total of 65 adult patients undergoing cardiac surgery were recruited to this clinical trial. A prophylactic cefazolin dose of 2 g was intravenously administered before surgery. Blood samples were collected using a rich sampling design and cefazolin serum concentrations were measured using the HPLC/UV method. The pharmacokinetic population model was calculated using a nonlinear mixed-effects modeling approach, and the Monte Carlo simulation was used to evaluate the PK/PD target attainment. The population cefazolin central volume of distribution (Vd) of 4.91 L increased by 0.51 L with each 1 m2 of BSA, peripheral Vd of 22.07 L was reduced by 0.77 L or 0.79 L when using ECC or MiECC support, respectively, while clearance started at 0.045 L/h and increased by 0.49 L/h with each 1 mL/min/1.73 m2 of eGFR. ECC/MiECC was shown to be covariate of cefazolin Vd, but without relevance to clinical practice, while eGFR was most influential for the PK/PD target attainment. The standard dose of 2 g was sufficient for PK/PD target attainment throughout surgery in patients with normal renal status or with renal impairment. In patients with augmented renal clearance, an additive cefazolin dose should be administered 215, 245, 288 and 318 min after the first dose at MIC of 4, 3, 2 and 1.5 mg/L, respectively. Full article
(This article belongs to the Special Issue Clinical Pharmacokinetics of Antibiotics)
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