Circadian variations in the pharmacokinetics of a new microemulsion formulation of cyclosporine in cardiac transplant recipients.

We attempted to characterize circadian variations in pharmacokinetic parameters of a new formulation of cyclosporine (CsA) in nine cardiac allograft recipients. A secondary objective was to determine the sampling time that correlated best with exposure of patients to the drug. This was a two-period study with each period lasting 12 hours. All patients received two equal doses of a new microemulsion of CsA 12 hours apart. Blood samples to measure drug levels were obtained at administration and 1, 2, 3, 4, 6, 9, and 12 hours after each dose. We found no statistically significant difference in pharmacokinetic parameters (areas under the curve, minimum blood concentration, oral clearance) measured during the day and during the night. However, maximum blood concentrations during the day were 30% higher than those at night (p<0.05). We found a good correlation between minimum concentrations in the morning and overall exposure of patients to CsA (r=0.89). This new microemulsion appears to have few circadian variations of blood concentrations in cardiac transplant recipients. The clinical significance of higher maximum blood concentration during daytime remains to be elucidated. Our results support the most widely accepted method for monitoring CsA, which is based on minimum concentrations in the morning.