[Pharmacokinetic significance of measurement of salivary penetration of protein-unbound pyridonecarboxylic acid antimicrobial agents].

The author attempted to determine the feasibility of monitoring blood concentration of antimicrobial agents by estimating blood levels of the agents on the basis of their content in saliva. Since it is difficult to determine drug tissue-penetration degree in humans, at present, tissue concentrations must be estimated from corresponding blood concentration. In the case of orally administered drugs exhibiting great individual differences in absorption by the gastrointestinal tract, frequent blood collection is required for blood-concentration monitoring. Noninvasive and very simple saliva collection, on the other hand, has already been used for monitoring concentrations of such drugs as carbamazepine and antiepileptics. PPA, ENX, NFLX, and OFLX are pyridonecarboxylic acid antimicrobial agents of great usefulness because of their expanded antimicrobial spectrum and their effectiveness even against gram-negative bacteria that exhibit no adequate response to other oral antimicrobial agents. After PPA, ENX, NFLX, and OFLX were administered orally to healthy volunteers, serum and saliva samples were collected. The samples were then centrifuged, deproteinized, and freeze-dried. 1. After the freeze-dried samples were dissolved to give tenfold to twentyfold concentrated solutions, levels of agents were bioassayed by means of the thin-layer-disc method. On the basis of the data obtained in this way, pharmacokinetic analyses were performed according to the one compartment model of Imoto and Yamaoka. A personal computer (NEC-8801, 9801) was used in drawing simulated curves. 2. Percentages of salivary as compared to serum concentrations were as follows: PPA (500 mg)-70, ENX (300 mg)-75, ENX (200 mg)-78, NFLX (200 mg)-35, and OFLX (200 mg)-105. Corresponding values for pharmacokinetic data were as follows: PPA (500 mg)-77.2, ENX (300 mg)-74.2, ENX (200 mg)-85.0, NFLX (200 mg)-30.0, and OFLX (200 mg)-91.6. Coefficients of correlation (r =) between salivary and serum concentrations in measured data were as follows: PPA (500 mg)-0.915, ENX (300 mg)-0.989, ENX (200 mg)-0.953, NFLX (200 mg)-0.887, and OFLX (200 mg)-0.886.(ABSTRACT TRUNCATED AT 400 WORDS)