The excretion of cephem antibiotics into saliva is inversely associated with their plasma protein-binding activities

BACKGROUND: The excretion of medicated drugs into saliva may disturb the oral environment and antibiotic excretion into saliva appears to be regulated by many factors that have not been fully explored. METHODS: Excretion of four cephem antibiotics into saliva was examined in healthy volunteers and rats, using high-performance liquid chromatography, and the relationship between excretion levels and plasma protein-binding activities of the antibiotics was investigated. RESULTS: Following addition of 50 microgram/ml of each antibiotic to human plasma, protein binding rates (PBRs) of cefuzonam (CZON, molecular weight (MW): 535.58), cefotaxime (CTX, MW: 477.45), flomoxef (FMOX, MW: 518.45) and cefozopran (CZOP, MW: 551.99) were 87.8 +/- 1.2, 70.8 +/- 0.8, 36.2 +/- 0.5 and 8.3 +/- 0.3%, respectively. In rat plasma, PBRs of the four antibiotics were 94.0 +/- 0.5, 62.1 +/- 1.4, 54.0 +/- 0.8 and 6.0 +/- 0.8%, respectively. Similar PBRs were observed when the antibiotic concentration was increased to 100 and 200 microgram/ml. CZOP was most rapidly excreted into saliva and had the highest concentration in saliva among the tested antibiotics, while the plateau level of CZON was the lowest. The excreted levels of each antibiotic in saliva, when locally perfused through the rat facial artery, were inversely associated with each PBR. Similarly, the ratios of antibiotic concentration in saliva to rat plasma were almost constant for each antibiotic, revealing an inverse relationship with PBRs. CONCLUSION: These results appear to indicate that low molecular weight antibiotics are excreted into saliva through passive diffusion, inversely relating to their PBRs, and that high concentrations of antibiotics in the saliva have the potential to change the oral ecological environment.