Brodimoprim concentrations in bronchial mucosa, bronchial secretions and middle ear effusions.
Brodimoprim, a structural analogue of trimethoprim, is a long acting broad spectrum antibacterial agent characterized by a good pharmacokinetic profile, allowing once daily (OD) administration. The aim of this study was to investigate the penetration of brodimoprim into bronchial mucosa, bronchial secretion and middle ear effusion, in order to evaluate the efficacy of the antibiotic in respiratory tract infections. The study was performed in patients affected by chronic bronchitis having to undergo diagnostic bronchoscopy (n = 26), in patients affected by exacerbation of chronic bronchitis with purulent or mucopurulent secretions (n = 10), and in patients affected by otitis media with eardrum perforation (n = 28). Patients were orally treated with 400 mg of brodimoprim (single dose). Samples of serum, bronchial mucosa, bronchial secretion and middle ear effusion were collected in the separate series of patients above mentioned, at different times after drug administration. Brodimoprim determinations were performed by a microbiological method using Bacillus subtilis ATCC 6633 as test microorganism. Brodimoprim reached the highest concentration in serum 4 h after administration and was still detectable at 24th hour. In bronchial mucosa and in bronchial secretion the peaks were reached at 8th hour (9.7 +/- 5.3 mg/kg and 4.57 +/- 1 mg/l respectively) while in middle car effusion were reached at 4th hour (4.8 +/- 2.5 mg/l). The drug was still detectable at antibacterial concentrations, both in infected fluids and in tissue samples, 24 hours after administration (4.3 +/- 1.8 mg/kg in bronchial mucosa; 3.5 +/- 0.66 mg/l in bronchial secretions; 3 +/- 0.6 mg/l in middle ear effusion).(ABSTRACT TRUNCATED AT 250 WORDS)
Scaglione
F
F
Dept. Pharmacology, Chemotherapy and Toxicology, University of Milan, Italy.
Cogo
R
R
Pintucci
J P
JP
Demartini
G
G
Dugnani
S
S
Maccarinelli
G
G
Fraschini
F
F
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001980:Bronchi / Q000378:metabolism*; D001991:Bronchitis / Q000188:drug therapy* / Q000378:metabolism*; D002908:Chronic Disease; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010034:Otitis Media with Effusion / Q000188:drug therapy* / Q000378:metabolism*; D014295:Trimethoprim / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018058:Tympanic Membrane Perforation / Q000188:drug therapy / Q000378:metabolism
D014295:Trimethoprim; C037079:brodimoprim