Rifampicin reduces plasma concentrations of moxifloxacin in patients with tuberculosis.
BACKGROUND
The long duration of the current tuberculosis (TB) treatment is demanding and warrants the development of new drugs. Moxifloxacin shows promising results and may be combined with rifampicin to shorten the duration of TB treatment. Rifampicin induces the phase II metabolic enzymes that are involved in the biotransformation of moxifloxacin. Therefore, the interaction between rifampicin and moxifloxacin should be investigated.


METHODS
Nineteen Indonesian patients with pulmonary TB who were in the last month of their TB treatment completed a 1-arm, 2-period, fixed-order pharmacokinetic study. In phase 1 of the study, they received 400 mg of moxifloxacin every day for 5 days in addition to 450 mg of rifampicin and 600 mg of isoniazid 3 times per week. In phase 2 of the study, after a 1-month washout period, patients received moxifloxacin for another 5 days (without rifampicin and isoniazid). A 24-h pharmacokinetic curve for moxifloxacin was recorded on the last day of both study periods, and its pharmacokinetic parameters were evaluated for an interaction with rifampicin, using a bioequivalence approach.


RESULTS
Coadministration of moxifloxacin with rifampicin and isoniazid resulted in an almost uniform decrease in moxifloxacin exposure (in 18 of 19 patients). The geometric means for the ratio of phase 1 area under the curve to phase 2 area under the curve and for the ratio of phase 1 peak plasma concentration to phase 2 peak plasma concentration were 0.69 (90% confidence interval, 0.65-0.74) and 0.68 (90% confidence interval, 0.64-0.73), respectively. The median time to reach peak plasma concentration for moxifloxacin was prolonged from 1 h to 2.5 h when combined with rifampicin and isoniazid (P=.003).


CONCLUSIONS
Coadministration of moxifloxacin with intermittently administered rifampicin and isoniazid results in reduced moxifloxacin plasma concentrations, which is most likely the result of induced glucuronidation or sulphation by rifampicin. Further studies are warranted to evaluate the impact of the interaction on the outcome of TB treatment.
Nijland
H M J
HM
Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. H.Nijland@akf.umcn.nl.
Ruslami
R
R
Suroto
A Juwono
AJ
Burger
D M
DM
Alisjahbana
B
B
van Crevel
R
R
Aarnoutse
R E
RE
D000293:Adolescent; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D007214:Indonesia; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D010949:Plasma / Q000737:chemistry*; D011804:Quinolines / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics*; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000904:Antibiotics, Antitubercular; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin; D007538:Isoniazid; D012293:Rifampin