Concentration of clarithromycin and 14-R-hydroxy-clarithromycin in plasma of patients with Mycobacterium avium complex infection, before and after the addition of rifampicin.
Clarithromycin (CAM) and rifampicin (RFP) have both been recognized to be effective antibiotic agents against Mycobacterium avium complex (MAC) infection. Rifamycin derivatives including RFP and rifabutin modulate the CAM metabolism by inducing the hepatic cytochrome p-450 3A4. To clarify the effect of RFP on the CAM metabolism, we measured the plasma concentration of CAM and 14-R-hydroxyclarithromycin (M-5), the major metabolite of CAM, in 9 patients suffering from MAC infection before and after the addition of RFP. After the addition of RFP, the mean plasma concentration of CAM significantly decreased, while that of M-5 did not. In addition, the amount of CAM + M-5 concentration also significantly decreased. As M-5 is less effective against MAC infection than CAM, more attention should thus be paid to the plasma CAM concentration in patients administered CAM and RFP concomitantly.
Yamamoto
F
F
Division of Internal Medicine, National Ohmuta Hospital.
Harada
S
S
Mitsuyama
T
T
Harada
Y
Y
Kitahara
Y
Y
Yoshida
M
M
Nakanishi
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood*; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000494:pharmacology*; D017291:Clarithromycin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000378:metabolism*; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
C487846:14-R-hydroxy-clarithromycin; D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D017291:Clarithromycin; D012293:Rifampin