Concentrations of clarithromycin and active metabolite in the epithelial lining fluid of patients with Mycobacterium avium complex pulmonary disease.
OBJECTIVE
Clarithromycin (CAM) is widely accepted for the treatment of Mycobacterium avium complex (MAC) pulmonary diseases. This study measured (a) the concentrations of CAM and its active metabolite (14OH-CAM) in bronchial epithelial lining fluid (ELF) obtained by bronchoscopic microsampling (BMS), and (b) the minimal inhibitory concentrations (MIC) of CAM for each MAC isolate.


METHODS
We studied eight patients with MAC pulmonary disease treated with oral CAM, 400 (n=4) or 800 (n=4) mg/day. BMS was performed 3h after the last CAM dose, and the concentrations of CAM and 14OH-CAM were measured in ELF collected from the diseased and normal contralateral pulmonary segments, and in serum.


RESULTS
The mean+/-SEM ELF concentrations of CAM (23.85+/-7.64 microg/ml) and CAM+14OH-CAM (28.71+/-8.37 microg/ml) in the 800 mg/day treatment group were significantly higher than in the 400mg/day group (7.48+/-2.58 microg/ml and 9.63+/-2.99 microg/ml, respectively; both p<0.05), while the serum concentrations were similar in both groups. In both treatment groups, the mean ELF concentrations sampled from diseased and normal segments were higher than the MIC against MAC isolates. The mean ELF concentration of CAM in the 400mg/day treatment group was <8 mircog/ml (the breakpoint concentration of CAM against M. avium recommended by the Clinical Laboratories Standards Institute), while the mean concentration in the 800 mg/day treatment group was >8 microg/ml.


CONCLUSIONS
These observations suggest that CAM, 800 mg/day, is an appropriate dose to treat MAC pulmonary disease, and prevent its spread from diseased to non-diseased lung segments.
Hasegawa
Naoki
N
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. hasegawn@sc.itc.keio.ac.jp
Nishimura
Tomoyasu
T
Watabnabe
Masazumi
M
Tasaka
Sadatomo
S
Nakano
Yasushi
Y
Yamazaki
Koichi
K
Hashimoto
Satoru
S
Nishimura
Masahiro
M
Ishizaka
Akitoshi
A
D000368:Aged; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001711:Biotransformation; D001826:Body Fluids / Q000378:metabolism; D015992:Body Mass Index; D001999:Bronchoscopy; D017291:Clarithromycin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D017291:Clarithromycin