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Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs

Sturkenboom, Marieke G. G., Märtson, Anne-Grete, Svensson, Elin M., Sloan, Derek, Dooley, Kelly E., van den Elsen, Simone H. J., Denti, Paolo, Peloquin, Charles A., Aarnoutse, Rob E. and Alffenaar, Jan-Willem C. (2021) 'Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs'. Clinical Pharmacokinetics, Vol 60, pp. 685-710.

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Tuberculosis (TB) is still the number one cause of death due to an infectious disease. Pharmacokinetics and pharmacodynamics of anti-TB drugs are key in the optimization of TB treatment and help to prevent slow response to treatment, acquired drug resistance, and adverse drug effects. The aim of this review was to provide an update on the pharmacokinetics and pharmacodynamics of anti-TB drugs and to show how population pharmacokinetics and Bayesian dose adjustment can be used to optimize treatment. We cover aspects on preclinical, clinical, and population pharmacokinetics of different drugs used for drug-susceptible TB and multidrug-resistant TB. Moreover, we include available data to support therapeutic drug monitoring of these drugs and known pharmacokinetic and pharmacodynamic targets that can be used for optimization of therapy. We have identified a wide range of population pharmacokinetic models for first- and second-line drugs used for TB, which included models built on NONMEM, Pmetrics, ADAPT, MWPharm, Monolix, Phoenix, and NPEM2 software. The first population models were built for isoniazid and rifampicin; however, in recent years, more data have emerged for both new anti-TB drugs, but also for defining targets of older anti-TB drugs. Since the introduction of therapeutic drug monitoring for TB over 3 decades ago, further development of therapeutic drug monitoring in TB next steps will again depend on academic and clinical initiatives. We recommend close collaboration between researchers and the World Health Organization to provide important guideline updates regarding therapeutic drug monitoring and pharmacokinetics/pharmacodynamics.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 268 Antitubercular agents. Antitubercular antibiotics
QV Pharmacology > QV 38 Drug action.
WC Communicable Diseases > WC 20 Research (General)
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):
Depositing User: Stacy Murtagh
Date Deposited: 09 Mar 2021 16:10
Last Modified: 05 Jul 2021 11:15


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