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In a recent study we investigated the in vivo effects of a seven day
treatment with 600 mg p.o. rifampicin once daily in the evening on the
pharmacokinetics of a putative OATP1B3-substrate (administered 12:00 hours
after the last dose rifampicin) in young healthy male and female volunteers.
This pre-treatment caused only slight inhibition of the substrate's
elimination, particularly in comparison with cyclosporine (one dose of 100
mg the evening before and one dose of 100 mg 1:00 hour before administration
of the substrate) or erythromycin (4-day treatment of 500 mg erythromycin
p.o. three times daily with the last dose administered 00:30 hour before
administration of the substrate).
Therefore we assume that the lack of effect of the rifampicin pre-treatment
is probably due to the 12:00 hour time lag between the last dose of
rifampicin and the administration of the OATP1B3-substrate.
I would appreciate suggestions for a better time schedule of the treatments
in such in vivo study in order to maximise the likelihood of identifying a
rifampicin-related inhibition of the OATP1B3-related elimination.
Many thanks - Christian de Mey
PD Dr. med. Christian de Mey
ACPS - Applied Clinical Pharmacology Services
Philippsring 11, D-55252 Mainz-Kastel, Germany
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