Serum and sputum concentrations of netilmicin in combination with acylureidopenicillin and cephalosporins in clinical treatment of pulmonary exacerbations in cystic fibrosis.
The pharmacokinetics of netilmicin was studied in 14 patients with cystic fibrosis, aged 4-21 years (mean 16 years) during treatment of pulmonary exacerbations of pseudomonas infection. The patients received 24 courses of netilmicin (10 mg/kg/day) in combination with azlocillin (600 mg/kg/day), cefsulodin (200 mg/kg/day) or ceftazidime (150 mg/kg/day) for 9-14 days. Seven patients received two or three courses of different combinations. Serum and sputum concentrations of netilmicin were determined on day 2 and 6. Mean (+/- S.E.M.) trough serum values were 1.4 +/- 0.2 mg/l (same on day 2 and 6), peak values at 10 min 13.6 +/- 1.0 and 13.7 +/- 0.9 mg/l, and serum concentration at 1 h 7.5 +/- 0.6 and 7.5 +/- 0.5 mg/l, on days 2 and 6 respectively. The half-life was about 1 h. The pharmacokinetics did not differ on day 2 and 6. Sputum concentrations increased up to 2-3 h after administration, mean (+/- S.E.M.) peak values being 2.6 +/- 0.6 and 1.5 +/- 0.4 mg/l at day 2 and 6, respectively. The study shows that the pharmacokinetics of netilmicin was not influenced by different combinations with beta-lactams. All patients improved clinically, but pseudomonas growth was only reduced in nine courses. In one case transient resistance to netilmicin developed during the treatment. The clinical efficacy and tolerance were good and similar to those seen with combinations with other aminoglycosides.
Hjelte
L
L
Department of Paediatrics, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Malmborg
A S
AS
Strandvik
B
B
D000293:Adolescent; D000328:Adult; D001390:Azlocillin / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D008297:Male; D009428:Netilmicin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013183:Sputum / Q000378:metabolism*
D002511:Cephalosporins; D009428:Netilmicin; D001390:Azlocillin