Pharmacokinetics of Levofloxacin and Capreomycin in Multidrug-Resistant Tuberculosis Patients

Pharmacokinetics of Levofloxacin and Capreomycin in MDR-TB Patients

This is an open label observational pharmacokinetic drug study to evaluate Levofloxacine and Capreomycin in patients with Multidrug-Resistant Tuberculosis (MDR-TB).

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Other: Pharmacokinetics

Detailed Description

Patients receive MDR-TB treatment with o.a. Levofloxacin and Capreomycin. At least one week after start of treatment, the PK samples samples will be obtained via an intravenous catheter at 0, 1, 2, 3, 4, 7, and 12 hours after intake.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus, 220053
    • Republican Scientific and Practical Center for TB and Pulmonology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

MDR-TB patients

Description

Inclusion Criteria:

• age> 18yrs
• culture positive
• diagnosis of MDR-TB

Exclusion Criteria:

• DM2
• Pregnancy
• allergy to IV canula material
• insertion of IV canula not possibele

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PK of Levofloxacin-Capreomycin; Pharmacokinetics (PK) in M/XDR-TB patients receiving at least Levofloxacin and Capreomycin as part of their WHO treatment for M/XDR-TB	Other: Pharmacokinetics; multiple blood samples are obtained by means of an indwelling intravenous catheter for calculating PK parameters

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC/MIC ratio of Levofloxacin	The primary outcome parameter is the ratio of the in vitro minimum inhibitory concentration (MIC) to the area under the serum concentration-time curve (AUC) over 24 hours (AUC0-24h ), [AUC0-24h /MIC], after administration of Levofloxacin.	after day 8 of treatment
Cmax/MIC ratio of Capreomycin	The primary outcome parameter is the ratio of the in vitro minimum inhibitory concentration (MIC) to the maximum serum concentration, [Cmax/MIC], after administration of Capreomycin.	after day 8 of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume of Distribution	Based on the measured drug concentration during the dosing interval and patient characteristics (height, bodyweight and age) the volume of distribution will be calculated	after day 8 of treatment
Clearance	Based on the drug concetrations during the dosing interval and patient characteristics (height, bodyweight, age) the drug clearance will be calculated	after day 8 of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK-model	A population PK model will be developed using an iterative 2-stage Bayesian procedure.	after day 8 of treatment
Limited sampling strategy	Limited sampling strategies were investigated subsequently using a Bayesian analysis. The best possible strategies for will be evaluated by a Bland-Altman analysis for correlation of predicted and observed AUC0-24.	after day 8 of treatment

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: National Institute for Public Health and the Environment (RIVM); Republican Scientific and Practical Centre for Pulmonology and TB
• Investigators: Principal Investigator: JW C Alffenaar, PhD PharmD, UMCG

Publications and helpful links

General Publications

• Van't Boveneind-Vrubleuskaya N, Seuruk T, van Hateren K, van der Laan T, Kosterink JGW, van der Werf TS, van Soolingen D, van den Hof S, Skrahina A, Alffenaar JC. Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant Tuberculosis Patients. Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00343-17. doi: 10.1128/AAC.00343-17. Print 2017 Aug.
• Velasquez AMA, Ribeiro WC, Venn V, Castelli S, Camargo MS, de Assis RP, de Souza RA, Ribeiro AR, Passalacqua TG, da Rosa JA, Baviera AM, Mauro AE, Desideri A, Almeida-Amaral EE, Graminha MAS. Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B. Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00688-17. doi: 10.1128/AAC.00688-17. Print 2017 Aug.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 23, 2014

Study Record Updates

• Last Update Posted (Estimate): June 23, 2014
• Last Update Submitted That Met QC Criteria: June 20, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: pharmacokinetics; Levofloxacin; pharmacodynamics; MDR-TB; Capreomycin
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: LC-20