Interaction of erythromycin and clarithromycin with orange juice

Edit
Abstract: Concomitant administration of orange juice with fexofenadine has been found to decrease the bioavailability of fenofenadine to less than  30%  via  inhibition  of  organic-anion  transporting  polypeptide  (OATP),  a  drug  uptake  transporter  expressed  in  organs  such  as liver, kidney and intestine. Erythromycin and clarithromycin are substrates and inhibitors of CYP3A4, a drug metabolizing enzyme in the  liver  and  enterocytes,  and  P-glycoprotein  (P-gp),  a  drug  efflux  transporter  expressed  in  the  same  organs  as  OATP.  Since  an extensive  overlap  exists  between  substrates  and  inhibitors  of  CYP3A4,  P-gp  and  OATP  transporters,  we  want  to  study  the  effect  of coadministration of our local orange (Siam orange) juice on the bioavailability of the above antibacterials. We conducted two 2-way cross-over randomized studies, one study for each antibacterial (500 mg), crossed between administration with orange juice (200 ml) and with water, in 12-13 healthy subjects per study. The serum concentrations of the antibacterials were assayed by microbiological method. The mean (range) ratio of AUC0-t with orange juice/with water were as follows : erythromycin : total (n=13) 81.7 (9.7-193.8)%, unchanged  (n=4)  96.4  (80.5-107.9)%,  decreased  (n=6)  31.9  (9.7-49.0)%,  increased  (n=3)  161.8  (134.6-193.8)%;  clarithromycin: total (n=12) 91.4 (20.6-158.3)%, unchanged (n=5) 103.1 (80.9-123.0)%, decreased (n=4) 34.8 (20.6-64.3)%, increased (n=3) 147.2 (132.9-158.3)%.  It  was  concluded  that  coadministration  of  Siam  orange  juice  with  erythromycin  or  clarithromycin  produced unpredictable effects on the bioavailability of these antibacterials in individual subjects, with marked decreases in almost  half of the subjects, although in totals the effects were not statistically significant.
Keywords: interaction, erythromycin, clarithromycin, orange juice
Author: Arini Setiawati, Metta Sinta Sari Wiria, Franciscus D. Suyatna, Juan Tjiu Sion, Marina Hamadian
Journal Code: jpkedokterangg050007

Artikel Terkait :

Jp Kedokteran gg 2005