BACKGROUND: Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug monitoring is not feasible in most settings. Developing a limited-sampling strategy based on population pharmacokinetics (PK) may help to overcome this problem. METHODS: Steady-state plasma concentrations after the administration of 400 mg of MFX once daily were determined in 21 patients with TB, using a validated liquid chromatography-tandem mass spectrometry method. A one-compartment population model was generated and crossvalidated. Monte Carlo data simulation (n=1000) was used to calculate limited-sampling strategies. The correlation between predicted MFX AUC0-24h (area under the concentration-time curve 0 to 24 hours) and observed AUC0-24h was investigated by Bland-Altman analysis. Finally, the predictive performance of the final model was tested prospectively using MFX profiles from patients with TB receiving 400, 600, or 800 mg once daily. RESULTS: Median minimum inhibitory concentration of Mycobacterium tuberculosis isolates was 0.25 mg/L (interquartile range: 0.25-0.5 mg/L). The geometric mean AUC0-24h was 24.5 mg·h/L (range: 8.5-72.2 mg·h/L), which resulted in a geometric mean AUC0-24h/minimum inhibitory concentration ratio of 72 (range: 21-321). PK analysis, based on PK profiles of 400 mg of MFX once daily, resulted in a crossvalidated population PK model with the following parameters: apparent clearance (Cl) 18.5±8.6 L/h per 1.85 m, Vd 3.0±0.7 L/kg corrected lean body mass, Ka 1.15±1.16 h, and F was fixed at 1. After the Monte Carlo simulation, the best predicting strategy for MFX AUC0-24h for practical use was based on MFX concentrations 4 and 14 hours postdosing (r=0.90, prediction bias=-1.5%, and root mean square error=15%). CONCLUSIONS: MFX AUC0-24h in patients with TB can be predicted with acceptable accuracy for clinical management, using limited sampling. AUC0-24h prediction based on 2 samples, 4 and 14 hours postdose, can be used to individualize treatment.
BACKGROUND:Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug monitoring is not feasible in most settings. Developing a limited-sampling strategy based on population pharmacokinetics (PK) may help to overcome this problem. METHODS: Steady-state plasma concentrations after the administration of 400 mg of MFX once daily were determined in 21 patients with TB, using a validated liquid chromatography-tandem mass spectrometry method. A one-compartment population model was generated and crossvalidated. Monte Carlo data simulation (n=1000) was used to calculate limited-sampling strategies. The correlation between predicted MFX AUC0-24h (area under the concentration-time curve 0 to 24 hours) and observed AUC0-24h was investigated by Bland-Altman analysis. Finally, the predictive performance of the final model was tested prospectively using MFX profiles from patients with TB receiving 400, 600, or 800 mg once daily. RESULTS: Median minimum inhibitory concentration of Mycobacterium tuberculosis isolates was 0.25 mg/L (interquartile range: 0.25-0.5 mg/L). The geometric mean AUC0-24h was 24.5 mg·h/L (range: 8.5-72.2 mg·h/L), which resulted in a geometric mean AUC0-24h/minimum inhibitory concentration ratio of 72 (range: 21-321). PK analysis, based on PK profiles of 400 mg of MFX once daily, resulted in a crossvalidated population PK model with the following parameters: apparent clearance (Cl) 18.5±8.6 L/h per 1.85 m, Vd 3.0±0.7 L/kg corrected lean body mass, Ka 1.15±1.16 h, and F was fixed at 1. After the Monte Carlo simulation, the best predicting strategy for MFX AUC0-24h for practical use was based on MFX concentrations 4 and 14 hours postdosing (r=0.90, prediction bias=-1.5%, and root mean square error=15%). CONCLUSIONS:MFX AUC0-24h in patients with TB can be predicted with acceptable accuracy for clinical management, using limited sampling. AUC0-24h prediction based on 2 samples, 4 and 14 hours postdose, can be used to individualize treatment.
Authors: S P van Rijn; M A Zuur; R van Altena; O W Akkerman; J H Proost; W C M de Lange; H A M Kerstjens; D J Touw; T S van der Werf; J G W Kosterink; J W C Alffenaar Journal: Antimicrob Agents Chemother Date: 2017-03-24 Impact factor: 5.191
Authors: Satria A Prabowo; Matthias I Gröschel; Ed D L Schmidt; Alena Skrahina; Traian Mihaescu; Serap Hastürk; Rotislav Mitrofanov; Edita Pimkina; Ildikó Visontai; Bouke de Jong; John L Stanford; Père-Joan Cardona; Stefan H E Kaufmann; Tjip S van der Werf Journal: Med Microbiol Immunol Date: 2012-11-10 Impact factor: 3.402
Authors: Simone H J van den Elsen; Marieke G G Sturkenboom; Onno W Akkerman; Katerina Manika; Ioannis P Kioumis; Tjip S van der Werf; John L Johnson; Charles Peloquin; Daan J Touw; Jan-Willem C Alffenaar Journal: Antimicrob Agents Chemother Date: 2019-06-24 Impact factor: 5.191
Authors: Robin J Svensson; Katarina Niward; Lina Davies Forsman; Judith Bruchfeld; Jakob Paues; Erik Eliasson; Thomas Schön; Ulrika S H Simonsson Journal: Br J Clin Pharmacol Date: 2019-07-25 Impact factor: 4.335
Authors: Marieke G G Sturkenboom; Leonie W Mulder; Arthur de Jager; Richard van Altena; Rob E Aarnoutse; Wiel C M de Lange; Johannes H Proost; Jos G W Kosterink; Tjip S van der Werf; Jan-Willem C Alffenaar Journal: Antimicrob Agents Chemother Date: 2015-06-08 Impact factor: 5.191