1. Longitudinal PKPD biomarkers correlate with treatment outcome in drug sensitive pulmonary tuberculosis; a population pharmacokinetic-pharmacodynamic analysis
- Author
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Kloprogge, Frank, Mwandumba, Henry C., Kamdolozi, Mercy, Banda, Gertrude, Shani, Doris, Corbett, Elizabeth L., Kontogianni, Nadia, Ward, Steve, Khoo, Saye H., Davies, Geraint R., Sloan, Derek James, University of St Andrews. School of Medicine, and University of St Andrews. Infection and Global Health Division
- Subjects
RM ,qw_541 ,NDAS ,qv_38 ,RM Therapeutics. Pharmacology ,Pharmacodynamics ,Standard treatment ,SDG 3 - Good Health and Well-being ,qv_268 ,RC Internal medicine ,Tuberculosis ,Pharmacokinetics ,wf_200 ,qy_120 ,Outcome ,RC - Abstract
Funding: Wellcome Trust Clinical PhD Fellowship awarded to D.S. (086757/Z/08/A). Funding for the minimum inhibitory concentration assays was provided by a grant from the British Society for Antimicrobial Chemotherapy (GA2015_036P). F.K. has conducted the research as part of his Medical Research Council fellowship (MR/P014534/1). Background . This study aims to explore relationships between baseline demographic covariates, plasma antibiotic exposure, sputum bacillary load, and clinical outcome data to help improve future tuberculosis (TB) treatment response predictions. Methods . Data were available from a longitudinal cohort study in Malawian drug-sensitive TB patients on standard therapy, including steady-state plasma antibiotic exposure (154 patients), sputum bacillary load (102 patients), final outcome (95 patients), and clinical details. Population pharmacokinetic and pharmacokinetic-pharmacodynamic models were developed in the software package NONMEM. Outcome data were analyzed using univariate logistic regression and Cox proportional hazard models in R, a free software for statistical computing. Results . Higher isoniazid exposure correlated with increased bacillary killing in sputum (P
- Published
- 2020