Abstract
Rabbits with catheters implanted in the left ventricle were given a single dose of moxalactam and sacrificed at various times thereafter for measurement of the concentration of this antimicrobial agent in serum, heart muscle, and various heart valves. Penetration into both extravascular sites was rapid; steady state was achieved within 5 min after the dose. Moxalactam showed essentially complete penetration into valve lesions, whereas concentrations in heart muscle were only 20% of those in serum. The physiological distribution of moxalactam in heart muscle was beyond the inulin space, but substantially lower than total body water. This myocardial distribution ratio was not predicted by the serum-free fraction or blood trapped in tissues alone, but was in good agreement with that of extracellular fluid plus blood trapped in tissues. The moxalactam distribution profile was most compatible with that of drugs which are excluded from cells but readily distributed throughout extracellular fluids. This explains its nearly complete penetration into heart valves as well as its incomplete penetration into heart muscle, since the two sites differ in their relative proportions of cells and extracellular fluid spaces.
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- Alexander J. W., Sykes N. S., Mitchell M. M., Fisher M. W. Concentration of selected intravenously administered antibiotics in experimental surgical wounds. J Trauma. 1973 May;13(5):423–434. doi: 10.1097/00005373-197305000-00004. [DOI] [PubMed] [Google Scholar]
- Barza M., Weinstein L. Penetration of antibiotics into fibrin loci in vivo. I. Comparison of penetration of ampicillin into fibrin clots, abscesses, and "interstitial fluid". J Infect Dis. 1974 Jan;129(1):59–65. doi: 10.1093/infdis/129.1.59. [DOI] [PubMed] [Google Scholar]
- Bergan T. Pharmacokinetics of tissue penetration of antibiotics. Rev Infect Dis. 1981 Jan-Feb;3(1):45–66. doi: 10.1093/clinids/3.1.45. [DOI] [PubMed] [Google Scholar]
- Brown K. N., Percival A. Penetration of antimicrobials into tissue culture cells and leucocytes. Scand J Infect Dis Suppl. 1978;(14):251–260. [PubMed] [Google Scholar]
- Carson H. B., Heller A. S., Koch T. B., Walczak P., Schentag J. J. Antibiotic penetration in abdominal infection: a case of tobramycin failure responsive to moxalactam. Drug Intell Clin Pharm. 1983 Apr;17(4):277–279. doi: 10.1177/106002808301700407. [DOI] [PubMed] [Google Scholar]
- Durack D. T., Beeson P. B. Experimental bacterial endocarditis. I. Colonization of a sterile vegetation. Br J Exp Pathol. 1972 Feb;53(1):44–49. [PMC free article] [PubMed] [Google Scholar]
- Gengo F. M., Schentag J. J. Methicillin distribution in serum and extravascular fluid and its relevance to normal and damaged heart valves. Antimicrob Agents Chemother. 1981 May;19(5):836–841. doi: 10.1128/aac.19.5.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gengo F. M., Schentag J. J. Rate of methicillin penetration into normal heart valve and experimental endocarditis lesions. Antimicrob Agents Chemother. 1982 Mar;21(3):456–459. doi: 10.1128/aac.21.3.456. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kunin C. M. Binding of antibiotics to tissue homogenates. J Infect Dis. 1970 Jan;121(1):55–64. doi: 10.1093/infdis/121.1.55. [DOI] [PubMed] [Google Scholar]
- Mandell G. L. Interaction of intraleukocytic bacteria and antibiotics. J Clin Invest. 1973 Jul;52(7):1673–1679. doi: 10.1172/JCI107348. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norrby R. A review of the penetration of antibiotics into CSF and its clinical significance. Scand J Infect Dis Suppl. 1978;(14):296–309. [PubMed] [Google Scholar]
- Perlman B. B., Freedman L. R. Experimental endocarditis. II. Staphylococcal infection of the aortic valve following placement of a polyethylene catheter in the left side of the heart. Yale J Biol Med. 1971 Oct;44(2):206–213. [PMC free article] [PubMed] [Google Scholar]
- Schentag J. J., Gengo F. M. Principles of antibiotic tissue penetration and guidelines for pharmacokinetic analysis. Med Clin North Am. 1982 Jan;66(1):39–49. doi: 10.1016/s0025-7125(16)31440-7. [DOI] [PubMed] [Google Scholar]
- Schentag J. J., Jusko W. J., Vance J. W., Cumbo T. J., Abrutyn E., DeLattre M., Gerbracht L. M. Gentamicin disposition and tissue accumulation on multiple dosing. J Pharmacokinet Biopharm. 1977 Dec;5(6):559–577. doi: 10.1007/BF01059684. [DOI] [PubMed] [Google Scholar]
- Weinstein L., Schlesinger J. J. Pathoanatomic, pathophysiologic and clinical correlations in endocarditis (first of two parts). N Engl J Med. 1974 Oct 17;291(16):832–837. doi: 10.1056/NEJM197410172911609. [DOI] [PubMed] [Google Scholar]
- Ziemniak J. A., Chiarmonte D. A., Miner D. J., Schentag J. J. HPLC determination of D and L moxalactam in human serum and urine. J Pharm Sci. 1982 Apr;71(4):399–402. doi: 10.1002/jps.2600710406. [DOI] [PubMed] [Google Scholar]