Bioequivalence and metabolism of nitrendipine administered orally to healthy volunteers.

Relative bioavailability of 5-, 10-, and 20-mg nitrendipine tablets was determined in a four-way crossover bioequivalence study involving 22 normal male volunteers. Liquid suspension of nitrendipine was used as a reference. Plasma and urine samples collected during each study period were assayed by high performance liquid chromatographic and capillary gas chromatographic (GC) procedures for nitrendipine and the nitrendipine pyridine metabolite. Four other more polar urinary nitrendipine metabolites were also analyzed in urine by the GC procedure, which involved diazomethane esterification. Although relative bioavailability of the tablets ranged from 58.0 to 69.9%, there was no statistically significant difference in the area under the curve among the doses. Since 35 to 43% of both the liquid and tablet doses was recovered in the urine of volunteers, excretion of urinary metabolites appears to be independent of the dosage form. However, a rank-order correlation between the relative tablet bioavailability and cumulative amounts of excreted metabolites was observed. Nitrendipine, its pyridine metabolite, and the glucuronide conjugates were also detected in the urine, but the amount of nitrendipine and its pyridine metabolite did not exceed 0.1% of dose, whereas the glucuronides accounted for about 8% of the dose.