Bioavailability of nalidixic acid from uncoated tablets in humans--Part I: Correlation with the dissolution rates of the tablets.

Bioavailabilities of three commercially available tablets and two trial tablets of nalidixic acid were determined. The correlation between in vivo bioavailability parameters and in vitro dissolution rates derived by eight methods (oscillating basket I and II, beaker I, II, and III, rotating basket, paddle and rotating flask) is discussed. Nalidixic acid and its metabolite, 7-hydroxynalidixic acid, were determined in serum by HPLC with a strong anion-exchange resin column. All parameters for nalidixic acid bioavailability showed significant differences among the tablets tested. The relationship between Cmax and AUC was not linear but concave. However, Cmax decreased linearly in proportion to the delay of Tmax. The rank order of tablets according to bioavailabilities was just the same as the rank order obtained when comparing dissolution rates determined by any of the above methods, with the exception of one tablet which had a poor disintegrating ability. The parameters for the rate of bioavailability (Cmax and Tmax) showed good linearity with 1/T50 determined by all of the methods. However, AUC showed significant correlation with neither T50 nor 1/T50.