Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence.

Some clinical studies require administration of test compounds in capsules to assure that the compound cannot be distinguished from a placebo. This raises the question of whether the pharmacokinetic responses produced by capsule administration are similar to values obtained when test compounds are ingested in solution. To test this, plasma phenylalanine and aspartate concentrations were compared in ten normal subjects ingesting 3 g aspartame in solution and in capsules in a balanced Latin square design. Peak plasma phenylalanine levels were significantly higher (191 +/- 65.4 v 117 +/- 39.5 mumol/L, mean +/- SD) and were reached significantly earlier (32 +/- 15 v 123 +/- 74 minutes) when aspartame was administered in solution than when it was administered in capsules. The area under the four-hour plasma phenylalanine concentration-time curve was significantly higher (15,340 +/- 4,820 v 8,465 +/- 3,356 mumol/L X min) when aspartame was ingested in solution. Administration in solution also produced a significantly higher ratio of plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids (0.36 +/- 0.12 v 0.23 +/- 0.06). Similarly, peak plasma aspartate concentrations were significantly higher 26.2 +/- 16.3 v 10.4 +/- 5.0 mumol/L) and were reached significantly earlier (30 +/- 14 v 106 +/- 61.3 min) when aspartame was administered in solution. The data indicate different plasma phenylalanine and aspartate pharmacokinetics between solution and capsule administration of aspartame.