Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis

Alffenaar, Jan Willem; Gumbo, Tawanda; Dooley, Kelly E.; Peloquin, Charles A.; McIlleron, Helen; Zagorski, Andre; Cirillo, Daniela María; Heysell, Scott K; Silva, Denise Rossato; Migliori, Giovanni Battista

doi:10.1093/cid/ciz942

Cited by 70 publications

(78 citation statements)

References 42 publications

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“…By implying multidisciplinary, multisectoral approaches, the new Global Tuberculosis Network (GTN) intends to research the much needed therapeutic and diagnostic requirements in the surge to eliminate TB upon applying PK. GTN indeed perceives and studies the existing knowledge slits and renders potential solutions as well (Alffenaar et al, 2019 ). Thus, our study will be the first to examine the PD implication toward the primary drug line CC of wild-type MIC on M. tuberculosis clinical isolates from South India.…”

Section: Discussionmentioning

confidence: 99%

Wild-Type MIC Distribution for Re-evaluating the Critical Concentration of Anti-TB Drugs and Pharmacodynamics Among Tuberculosis Patients From South India

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Wild-Type MIC Distribution for Re-evaluating the Critical Concentration of Anti-TB Drugs and Pharmacodynamics Among Tuberculosis Patients From South India

et al. 2020

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“…Hollow fiber infection models have been very useful to explore PK/PD relationships as it is possible to simulate human concentration–time profiles, and test different dosing strategies [ 5 ]. Although hollow fiber infection models have limitations, i.e., a lack of human immune response and a maximum number of drugs that can be tested simultaneously, the results correlate well with treatment response [ 6 ], which resulted in endorsement by the European Medicines Agency to make use of these models to guide dose selection for clinical trials [ 7 ].…”

Section: Pharmacokinetics and Pharmacodynamics Of Anti-tb Drugsmentioning

confidence: 99%

“…Here, it must be addressed that individual MIC values might not always be reliable and often are not available early in treatment. Moreover, MIC values might be significantly different when using different methods (e.g., solid or liquid media) [ 5 , 12 , 13 ]. This has important implications for the interpretation of AUC 0–24 h /MIC target values when taking into account how the MIC was determined in that study.…”

Section: Tdm and Dose Adjustmentmentioning

confidence: 99%

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

et al. 2021

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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.

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“…These devices tend to be user friendly and require a minimum of laboratory skills, which could deliver TDM to a large group of patients that otherwise would not have benefited from traditional TDM programmes. 30 The aim of this study was therefore to develop a simple, low-cost, robust assay using mobile spectrophotometry to quantify levofloxacin in human saliva that would be applicable for TDM in TB endemic settings.…”

Section: Introductionmentioning

confidence: 99%

A mobile microvolume UV/visible light spectrophotometer for the measurement of levofloxacin in saliva

Alffenaar

Jongedijk

Winkel

et al. 2020

Journal of Antimicrobial Chemotherapy

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Introduction Therapeutic drug monitoring (TDM) for personalized dosing of fluoroquinolones has been recommended to optimize efficacy and reduce acquired drug resistance in the treatment of MDR TB. Therefore, the aim of this study was to develop a simple, low-cost, robust assay for TDM using mobile UV/visible light (UV/VIS) spectrophotometry to quantify levofloxacin in human saliva at the point of care for TB endemic settings. Methods All experiments were performed on a mobile UV/VIS spectrophotometer. The levofloxacin concentration was quantified by using the amplitude of the second-order spectrum between 300 and 400 nm of seven calibrators. The concentration of spiked samples was calculated from the spectrum amplitude using linear regression. The method was validated for selectivity, specificity, linearity, accuracy and precision. Drugs frequently co-administered were tested for interference. Results The calibration curve was linear over a range of 2.5–50.0 mg/L for levofloxacin, with a correlation coefficient of 0.997. Calculated accuracy ranged from –5.2% to 2.4%. Overall precision ranged from 2.1% to 16.1%. Application of the Savitsky–Golay method reduced the effect of interferents on the quantitation of levofloxacin. Although rifampicin and pyrazinamide showed analytical interference at the lower limit of quantitation of levofloxacin concentrations, this interference had no implication on decisions regarding the levofloxacin dose. Conclusions A simple UV/VIS spectrophotometric method to quantify levofloxacin in saliva using a mobile nanophotometer has been validated. This method can be evaluated in programmatic settings to identify patients with low levofloxacin drug exposure to trigger personalized dose adjustment.

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Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis

Cited by 70 publications

References 42 publications

Wild-Type MIC Distribution for Re-evaluating the Critical Concentration of Anti-TB Drugs and Pharmacodynamics Among Tuberculosis Patients From South India

Wild-Type MIC Distribution for Re-evaluating the Critical Concentration of Anti-TB Drugs and Pharmacodynamics Among Tuberculosis Patients From South India

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

A mobile microvolume UV/visible light spectrophotometer for the measurement of levofloxacin in saliva

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