Dra. Samiksha Ghimire - Postdoctoral researcher, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, the Netherlands
"Pharmacokinetic/pharmacodynamic- based dose optimization of anti-TB drugs: what do we know?"
In addition to the selection of the appropriate drug, the optimization of antimicrobial therapy in Tuberculosis has two pillars: pharmacokinetics and pharmacodynamics. Pharmacokinetics (PK) describes the behavior of a drug in the patient’s body. Pharmacodynamics (PD) describes the effect of drug on the Mycobacterium tuberculosis (efficacy) and on the patient (toxicity). Integration of PK and PD (PK/PD) links a PK parameter together with minimum inhibitory concentration (MIC) such as AUC0-24/MIC, Cmax/MIC, Cmin/MIC or T%>MIC to the clinical effect. Then, the optimal dose and dosing frequency is determined based on the probability of target attainment for maximum kill of Mtb bacilli or prevention of resistance. A relatively fair agreement exists in PK/PD parameter between pre-clinical (hollow fiber infection model studies and animal studies) and clinical studies.
In recent years, great strides have been made in finding the PK/PD target for core anti-TB drugs (isoniazid, rifampicin, moxifloxacin, levofloxacin etc.). These drugs exhibit considerable pharmacokinetic variability. The inter-individual pharmacokinetic variabilities in combination with differences in microbial susceptibility means that patients on same standardized doses achieve a range of concentrations which can translate into different clinical outcomes. This is the reason, why some patients get cured while others fail the intensive TB treatment and possibly relapse later.
In this seminar, Dr. Ghimire will discuss how the PK/PD target can be utilized in the clinic for individual dose optimization through therapeutic drug monitoring and quantitative drug susceptibility testing. Furthermore, this talk will review the current evidence on possibilities of PK/PD based dose optimization of anti-TB drugs and highlight the challenges and knowledge gaps.
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