Higher doses of rifampicin as a means of more efficient use of this pivotal TB drug has shown promising results and might become standard in future. This means that higher doses of rifampicin will be co-administered with many other drugs taken by TB patients, including anti-retroviral, anti-diabetic, cardiovascular and other drugs. Therefore, in this study the aim is to quantitatively assess the drug interaction potential of high dose rifampicin (\~40 mg/kg daily dose, the currently available maximum tolerated dose) with respect to five major human drug-metabolizing CYP enzymes and P-gp in comparison to the conventional dose of 10 mg/kg daily in pulmonary TB patients. A phenotyping approach with single administration of several selective substrates for multiple enzymes will be used, in order to prevent multiple drug-drug interaction studies.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
25
A single dose of a cocktail of phenotyping probe drugs (caffeine, tolbutamide, omeprazole, dextromethorphan, midazolam and digoxin) will be administered together with standard dose rifampicin and 40 mg/kg rifampicin, respectively. Blood samples will be taken to assess phenotyping metrics of the cocktail agents and rifampicin pharmacokinetic parameters. The effect of high and standard dose rifampicin on the phenotyping metrics of the cocktail agents will be compared by using the bioequivalence approach
A single dose of a cocktail of phenotyping probe drugs (caffeine, tolbutamide, omeprazole, dextromethorphan, midazolam and digoxin) will be administered together with standard dose rifampicin and 40 mg/kg rifampicin, respectively. Blood samples will be taken to assess phenotyping metrics of the cocktail agents and rifampicin pharmacokinetic parameters. The effect of high and standard dose rifampicin on the phenotyping metrics of the cocktail agents will be compared by using the bioequivalence approach
TASK
Cape Town, South Africa
UCT lung institute
Cape Town, South Africa
area under the curve
area under the curve of probe drugs
Time frame: 24 hours
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