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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.

antimicrobial agents and chemotherapy

Moxalactam penetration into normal heart valve, cardiac vegetations, and myocardium in relation to protein binding and physiological distribution spaces