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The inter- and intraindividual variability of cyclosporine pharmacokinetics from a microemulsion formulation were compared with the currently marketed formulation in a sequential bioreplication study. Twenty-four healthy male volunteers were randomized to receive each formulation on two separate occasions; the reference treatment was a single oral dose of 300 mg of Sandimmune and the test treatment was a single oral dose of 180 mg of Sandimmune Neoral, both given as soft gelatin capsules. Serial venous blood samples were obtained over a period of 48 h after each administration, and cyclosporine concentrations were measured in whole blood by a specific monoclonal RIA method. Between- and within-subject variabilities were quantified from the appropriate sums of squares from analysis of variance and statistically compared between formulations. Both inter- and intraindividual variation for the peak concentration, time to reach the peak, area under the curve, and terminal half-life of the test formulation were significantly reduced (p0.05) with two exceptions. For area under the curve between subjects (p0.2) and peak concentration within subjects (p0.1), trends toward reduced variability for the test formulation were evident. These results were further reflected in the inter- and intraindividual coefficients of variation of the pharmacokinetic parameters that ranged from 3 to 22% for the test formulation compared with 19 to 41% for the reference formulation. In comparison with the currently marketed formulation, reduced variability in the pharmacokinetics of cyclosporine following oral administration of Sandimmune Neoral provides a more predictable and consistent concentration-time profile.