EFFECT OF POLYASPARTIC ACID ON PHARMACOKINETICS OF GENTAMICIN AFTER SINGLE INTRAVENOUS DOSE IN THE DOG

The effects of poly-L-aspartic acid on the pharmacokinetics of gentami cin were examined by using a randomized crossover trial design with th e dog. When analyzed according to a three-compartment open model, poly -L-aspartic acid reduced some first-order rate equation constants (A(3 ), lambda(1), and lambda(3)), the deep peripheral compartment exit mic roconstant (k(31)), the elimination rate constant (k(el)), and the are a under the concentration-time curve from 0 to 480 h (AUC(0-480)) (0.2 1-, 0.60-, 0.26-, 0.27-, 0.72-, and 0.76-fold, respectively; P < 0.05) but increased the volume of distribution at steady state (V-ss), the volume of distribution calculated by the area method (V-area), the app arent volume of the peripheral compartment (V-p), and all mean time pa rameters. These results suggested that poly-L-aspartic acid increased the distribution of gentamicin to or binding within the deep periphera l compartment and that poly-L-aspartic acid may have delayed gentamici n transit through the peripheral tissues. In contrast, poly-L-aspartic acid did not alter pharmacokinetic parameters relevant to the central or shallow peripheral compartments to a clinically significant extent . Although gentamicin's pharmacokinetic parameters of relevance to the rapeutic drug monitoring were not directly altered, this study has pro vided pharmacokinetic evidence that poly-L-aspartic acid alters the pe ripheral distribution of gentamicin. This pharmacokinetic interaction occurred after a single intravenous dose of each drug. Therefore, this interaction should be investigated further, before polyaspartic acid can be considered for use as a clinical nephroprotectant.