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Predition of tissue penetration parameters fo beta-lactam antibiotics - A literature and simulation-based study

Terrmin

HT21

Beskrivning

We're exploring how therapeutic drug monitoring (TDM) could be optimally performed for antibiotic combinations with a focus on associations of ?-lactam/?-lactamase inhibitor. In this work we compute the overall probability of target attainment (PTA) at the site of infection: for example PTA for the ?-lactam alone, PTA for the ?-lactamase inhibitor and PTA for the combo.

In order to compute PTA at the different sites of infection we need penetration ratios from the literature.
We found a way around that, which would require us to calculate tissue-to-plasma partition coefficient (Kp) for each organ, for each drug (through the use of Physiology-Based PK, PBPK).
The project would involve collection of PK parameters and values from the literature for each drug of each combo (ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, meropenem-vaborbactam and piperacillin-tazobactam) and once all parameters required are known: use a PBPK model to compute the different Kp coefficients. These parameters would later use in our PTA simulations.

Huvudområde

Farmaceutisk vetenskap

Ämne

Farmakokinetik

Typ

Litteraturstudie

Företag

Uppsala Universitet

Ort/Plats

BMC, Uppsala

Handledarens namn

Amaury O´Jeanson

Handledarens e-post

amaury.ojeanson@farmaci.uu.se

Institution

Program

Kurs

Omfattning/hp

30hp

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1

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