Author:
Dudley M N,Levitz R E,Quintiliani R,Hickingbotham J M,Nightingale C H
Abstract
The pharmacokinetics of trimethoprim (TMP) and sulfamethoxazole (SMX) in cerebrospinal fluid (CSF) and serum after a single intravenous infusion of 5 mg of TMP and 25 mg of SMX per kg of body weight over approximately 120 min were studied i nine patients who had uninflamed meninges and were undergoing elective myelography. Peak concentrations of TMP and SMX in CSF were 1 microgram/ml and 13.8 micrograms/ml, respectively. The peak TMP concentration in CSF occurred significantly earlier than the peak SMX concentration (60 versus 480 min postinfusion). At 15 h, there was no detectable TMP in the CSF, and there was 4.7 micrograms of SMX per ml of CSF. In the postdistribution phase (in CSF), simultaneous CSF-to-serum concentration ratios ranged from 0.23 to 0.53 for TMP and from 0.20 to 0.36 for SMX. CSF penetration (measured by comparison of the area under the curve of the composite CSF and serum concentration-time curves) was 18% for TMP and 12% for SMX. A loading dose of TMP-SMX (bases on TMP) of 10 to 12 mg/kg and a maintenance dose of 6 mg/kg every 8 h or 8 mg/kg every 12 h (with a 2-h infusion) should yield steady-state peak concentrations of at least 5 micrograms of TMP per ml of serum and 160 micrograms of SMX per ml of serum. Further studies of TMP-SMX administered in these doses in the treatment of serious bacterial infection, including meningitis, are warranted.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference29 articles.
1. Intravenous trimethoprim-sulfamethoxazole in the treatment of serious infections in children;Ardati K. O.;J. Pediatr.,1979
2. Evaluation of the therapeutic activity and measurement of dosage of Bactrim injectable in children with healthy meninges and in children suffering from purulent meningitis;Blanc Pardigon M.;Med. Actuelle.,1977
3. Use of trimethoprim-sulfamethoxazole for treatment of infections in patients with cancer;Body B. P.;Rev. Infect. Dis.,1982
4. Boger W. P. and J. J. Gavin. 1960. Sulfamethoxazole: comparison with sulfisoxazole and sulfaethidole and cerebrospinal fluid diffusion. Antibiot. Chemother. (Washington D.C.) 10:573-580.
5. Parenteral trimethoprim-sulfamethoxazole and carbenicillin as empiric therapy for neutropenic patients with cancer;Braine H. G.;Rev. Infect. Dis.,1982
Cited by
59 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献