Bioavailability of tolazamide from tablets: comparison of in vitro and in vivo results.

The relative bioavailability of tolazamide was determined, in healthy male volunteers, from four different tablet formulations manufactured by direct compaction or granulation processes and the results were compared with in vitro disintegration and dissolution values. Serum tolazamide levels were determined by a high-pressure liquid chromatographic method developed in this laboratory. Serum tolazamide levels from the formulation that gave rise to rapid absorption were described by one-compartment model kinetics with a mean absorption half-time of 1.0 hr and an elimination half-life of 4.6 hr. Peak serum levels occurred at 3.3 hr after drug administration. Marked differences were observed in drug bioavailability from the four tablets, and the mean cumulative relative fraction of dose absorbed was 1.0, 0.42, 0.75, and 0.91 from Formulations A, B, C, and D, respectively. The hypoglycemic effect was closely related to serum tolazamide levels. Disintegration times did not predict in vivo tolazamide bioavailability. Dissolution rates provided an approximate rank order correlation with in vivo absorption but failed to be predictive among formulations. Currently available in vitro tests do not accurately predict tolazamide in vivo bioavailability characteristics among different formulations and manufacturing processes but may be useful to ensure lot-to-lot uniformity in bioavailability for a given formulation and specific method of manufacture.