Author: Cornelia Landersdorfer

Semi-mechanistic modelling of ceftolozane/tazobactam plus tobramycin against planktonic and biofilm bacteria of hypermutable Pseudomonas aeruginosa epidemic strains

Akosua Agyeman (1), Carla López-Causapé (2,3), Kate Rogers (1), Deanna Deveson Lucas (1), Sara Cortés-Lara (2,3), Maria Gomis-Font (2,3), Pablo Fraile-Ribot (2,3), Joan Figuerola (2), Yinzhi Lang (4), Eva Franklyn (1), Wee Leng Lee (1), Jieqiang Zhou (4), Yongzhen Zhang (4), Jurgen Bulitta (4), John Boyce (1), Roger Nation (1), Antonio Oliver (2,3), Cornelia Landersdorfer (1)
1. Monash University, 2. Hospital Universitario Son Espases, 3. CIBER Enfermedades Infecciosas, 4. University of Florida

Background: Biofilm-associated Pseudomonas aeruginosa infections in cystic fibrosis have limited treatment options. Ceftolozane/tazobactam is a relatively recently available β-lactam/β-lactamase inhibitor combination that has been shown to have preserved activity against difficult-to-treat P. aeruginosa isolates. However, the effectiveness of ceftolozane/tazobactam (C/T), in monotherapy and combination with tobramycin (TOB), has not yet been characterised for the pharmacokinetics […]

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Population modelling of lithium in paediatric patients with bipolar disorder: implications for dosing

Cornelia B Landersdorfer (1), Robert L Findling (2), Perdita Taylor-Zapata (3), Carl M J Kirkpatrick (1).
1. Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC, AUS; 2. Child and Adolescent Psychiatry, Johns Hopkins University, Baltimore, MD, USA; 3. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, USA;

Introduction. Bipolar I disorder (BP-I) leads to substantive psychosocial dysfunction. Lithium is well-established for treating BP-I in adults, however there is a paucity of information in paediatrics. Aims. To characterise the pharmacokinetics/pharmacodynamics (PK/PD) of lithium in paediatrics and to predict lithium concentrations and clinical effects for novel dosage regimens. Methods. Observed lithium concentrations and Young […]

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Population pharmacokinetics of colistin and its prodrug colistin methanesulfonate following intravenous and pulmonary dosing in sheep

Cornelia B Landersdorfer (1), Tri-Hung Nguyen (2), LT Lieu (2), RJ Bischof (3), Michelle P McIntosh (2).
1. Centre for Medicine Use and Safety, Monash University, Parkville, VIC, Australia; 2. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia; 3. Biotechnology Research Laboratories, School of Biomedical Sciences, Monash University, Clayton, VIC, Australia;

Background. Colistin is administered as its inactive prodrug colistin methanesulfonate (CMS) and is increasingly used as last-line therapy against multidrug-resistant Gram-negative bacteria. While pulmonary dosing of CMS is utilised in lung infections to reduce the risk of nephrotoxicity and neurotoxicity, there is a dearth of pharmacokinetic (PK) information on colistin and CMS. Quantitatively characterising the […]

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Mechanism-based modelling and sequential dosing to elucidate subpopulation synergy for antibiotic combinations

Cornelia B Landersdorfer (1,2), Neang S Ly (2), Hongmei Xu (2), Brian T Tsuji (2), Jurgen B Bulitta (1,2).
1. Centre for Medicine Use and Safety, Monash University, Parkville, VIC, Australia; 2. School of Pharmacy and Pharmaceutical Sciences, SUNY Buffalo, NY, USA;

Background: Rational and prospective approaches to optimize antibiotic combination therapy are scarce. Due to the emerging global healthcare crisis caused by multidrug-resistant bacteria, more efficient and quantitative approaches to optimize combination therapy are urgently required. Nisin, a peptide antibiotic affecting pore formation in bacterial membranes and preventing peptidoglycan synthesis, is rapidly bactericidal against multiple-resistant Staphylococcus […]

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Population Modelling of Vildagliptin as an Inhibitor and Substrate of Dipeptidylpeptidase IV and its Effects on Glucagon-Like Peptide 1, Glucose, and Insulin

Cornelia B Landersdorfer (1,2), Yan-Ling He (3), William J Jusko (2)
(1) Centre for Medicine Use and Safety, Monash University, Parkville, VIC, (2) School of Pharmacy and Pharmaceutical Sciences, SUNY Buffalo, NY, USA;, (3) Translational Science-Translational Medicine, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.

Background. Vildagliptin acts by inhibiting dipeptidyl peptidase IV (DPP-4), thereby increases active GLP-1 (glucagon-like peptide 1) concentrations and decreases plasma glucose in diabetic patients. Objectives. To develop a mechanism-based population PK/PD model that simultaneously describes and predicts vildagliptin pharmacokinetics and its effects on DPP-4 activity and the underlying glucose-insulin-GLP-1 system. Methods. Data used for model […]

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