The relative bioavailability of a 200 mg film-coated tablet of [12C]moricizine.HCl in comparison to a 200 mg [13C6]moricizine.HCl oral solution was determined after simultaneous administration to 8 young healthy male subjects. Concentrations of [12C]moricizine.HCl and [13C6]moricizine.HCl were determined by thermospray liquid chromatography-mass spectrometry (LC-MS) using [2H11]moricizine.HCl as the internal standard. The mean absorption and disposition parameters of the tablet versus the solution were the following (%CV): maximum concentration, 0.83 (39%) versus 0.79 (39%) microgram/mL; time of maximum concentration, 0.81 (40%) versus 0.65 (28%) hours; area under the concentration-time curve (AUC), 1.58 (39%) versus 1.49 (37%) micrograms.h/mL; apparent oral clearance, 150.7 (52%) versus 158.1 (50%) L/h; and t1/2, 1.9 (42%) versus 1.9 (42%) hours. The AUC for the tablet averaged 106% of the solution, which likely reflects a greater first-pass effect with the oral solution. Partitioning sources of variation confirmed the low (< 6%) intrasubject coefficient of variation (cv epsilon) afforded via the single-period, dual-isotope design. In contrast, a previous study using the conventional two-period crossover design determined the cv epsilon about moricizine metrics to be in excess of 30%, resulting in classification of this drug as having highly variable absorption. The results of this study further illustrate the benefits of dual, stable isotopes to assess bioavailability and bioequivalence. This paradigm results in a reduction in experimental time and subject inconvenience and lower costs in comparison with the standard crossover study. Perhaps most important is the improved statistical power for the evaluation of bioavailability or bioequivalence in the absence of period and sequence effects that confound the assessment of intrasubject variation in the standard crossover design.