EFFECT OF RIFABUTIN ON ETHAMBUTOL PHARMACOKINETICS IN HEALTHY VOLUNTEERS

The effect of repeated administration of rifabutin on the pharmacokinetics and metabolism of ethambutol was evaluated in ten healthy volunteers. The subjects received a single oral administration of 1200 mg ethambutol on days 1 and 10 and a single daily oral dose of 300 mg rifabutin from days 3 to 9...

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Published inPharmacological research Vol. 40; no. 4; pp. 351 - 356
Main Authors BREDA, M., BENEDETTI, M.STROLIN, BANI, M., PELLIZZONI, C., POGGESI, I., BRIANCESCHI, G., ROCCHETTI, M., DOLFI, L., SASSELLA, D., RIMOLDI, R.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.10.1999
Subjects
Adult
Antibiotics, Antitubercular - blood
Antibiotics, Antitubercular - pharmacology
Antitubercular Agents - blood
Antitubercular Agents - pharmacokinetics
Antitubercular Agents - urine
Drug Therapy, Combination
Ethambutol - blood
Ethambutol - pharmacokinetics
Ethambutol - urine
Humans
Male
Middle Aged
Rifabutin - blood
Rifabutin - pharmacology
rifabutin, ethambutol, pharmacokinetics, drug interaction
rifabutin, ethambutol, pharmacokinetics, drug interaction
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Summary:The effect of repeated administration of rifabutin on the pharmacokinetics and metabolism of ethambutol was evaluated in ten healthy volunteers. The subjects received a single oral administration of 1200 mg ethambutol on days 1 and 10 and a single daily oral dose of 300 mg rifabutin from days 3 to 9. No statistically significant difference was found in plasma pharmacokinetics (Cmax, tmax, AUC, half-life and MRT) and in the renal clearance, whereas a significant decrease in the amount of unchanged ethambutol excreted in urine was observed. The decrease observed in ethambutol urinary excretion may be accounted for by taking into consideration the variability of the urinary excretion of ethambutol reported in the literature. However, a slight, likely not clinically relevant, induction or activation of kidney alcohol and/or aldehyde dehydrogenase isoenzymes by rifabutin cannot be ruled out at present. Evidence exists in the present study for autoinduction of rifabutin metabolism; this is shown by the lower plasma concentrations obtained 24 h after the seventh dose as compared to the theoretical concentrations.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1043-6618
1096-1186
DOI:10.1006/phrs.1999.0526