Tuberculosis
Conditions
Keywords
pharmacokinetics, pharmacodynamics, MDR-TB, Levofloxacin, Capreomycin
Brief summary
This is an open label observational pharmacokinetic drug study to evaluate Levofloxacine and Capreomycin in patients with Multidrug-Resistant Tuberculosis (MDR-TB).
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.
Interventions
OTHERPharmacokinetics
multiple blood samples are obtained by means of an indwelling intravenous catheter for calculating PK parameters
Sponsors
Republican Scientific and Practical Centre for Pulmonology and TB
National Institute for Public Health and the Environment (RIVM)
University Medical Center Groningen
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC/MIC ratio of Levofloxacin | after day 8 of treatment | 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. |
| Cmax/MIC ratio of Capreomycin | after day 8 of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of Distribution | after day 8 of treatment | Based on the measured drug concentration during the dosing interval and patient characteristics (height, bodyweight and age) the volume of distribution will be calculated |
| Clearance | after day 8 of treatment | Based on the drug concetrations during the dosing interval and patient characteristics (height, bodyweight, age) the drug clearance will be calculated |
Other
| Measure | Time frame | Description |
|---|---|---|
| PK-model | after day 8 of treatment | A population PK model will be developed using an iterative 2-stage Bayesian procedure. |
| Limited sampling strategy | after day 8 of treatment | 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. |
Countries
Belarus
Outcome results
None listed