Publication

Limited sampling strategies using linear regression and the Bayesian approach for therapeutic drug monitoring of moxifloxacin in tuberculosis patients

van den Elsen, S. H. J., Sturkenboom, M. G. G., Akkerman, O. W., Manika, K., Kioumis, I. P., van der Werf, T. S., Johnson, J. L., Peloquin, C., Touw, D. J. & Alffenaar, J-W. C., 22-Apr-2019, In : Antimicrobial Agents and Chemotherapy. 38 p.

Research output: Contribution to journalArticleAcademicpeer-review

Copy link to clipboard

Documents

  • Limited sampling strategies using linear regression and the Bayesian approach for therapeutic drug monitoring of moxifloxacin in tuberculosis patients

    Final author's version, 1 MB, PDF-document

    Embargo ends: 22/10/2019

DOI

Therapeutic drug monitoring (TDM) of moxifloxacin is recommended to improve response to tuberculosis treatment and reduce acquired drug resistance. Limited sampling strategies (LSSs) are able to reduce the burden of TDM by using a small number of appropriately timed samples to estimate the parameter of interest; the area under the concentration time curve. This study aimed to develop LSSs for moxifloxacin alone (MFX) and together with rifampicin (MFX+RIF) in TB patients.Population pharmacokinetic (popPK) models were developed for MFX (n=77) and MFX+RIF (n=24). Additionally, LSSs using Bayesian approach and multiple linear regression were developed. Jackknife analysis was used for internal validation of the popPK models and multiple linear regression LSSs. Clinically feasible LSSs (1-3 samples; 6 h timespan post-dose; 1 h interval) were tested.Moxifloxacin exposure was slightly underestimated in the one compartment models of MFX (mean -5.1%, standard error [SE] 0.8%) and MFX+RIF (mean -10%, SE 2.5%). The Bayesian LSSs for MFX and MFX+RIF (both 0 and 6 h) slightly underestimated drug exposure (MFX mean -4.8%, SE 1.3%; MFX+RIF mean -5.5%, SE 3.1%). The multiple linear regression LSS for MFX (0 and 4 h) and MFX+RIF (1 and 6 h), showed a mean overestimation of 0.2% (SE 1.3%) and 0.9% (SE 2.1%), respectively.LSSs were successfully developed using the Bayesian approach (MFX and MFX+RIF; 0 and 6 h) and multiple linear regression (MFX 0 and 4 h, MFX+RIF 1 and 6 h). These LSSs can be implemented in clinical practice to facilitate TDM of moxifloxacin in TB patients.

Original languageEnglish
Number of pages38
JournalAntimicrobial Agents and Chemotherapy
Publication statusE-pub ahead of print - 22-Apr-2019

View graph of relations

ID: 81818289