Cyclosporine Pharmacokinetics and Variability From a Microemulsion Formulation—a Multicenter Investigation in Kidney Transplant Patients

Cyclosporine Microemulsion (Neoral®) Absorption Profiling and Sparse-sample Predictors During the First 3 Months after Renal Transplantation

“…The microemulsion formulation of CsA (Neoral TM , Novartis Pharma, Basle, Switzerland), which provides enhanced absorption with relative independence from the effects of food, bile flow and gastrointestinal dysfunction, resulting in lower inter-and intraindividual variability of exposure, offers an important opportunity to optimize this approach (7)(8)(9)(10)(11). CsA concentration monitoring is normally performed using a single pre-dose specimen to measure whole blood 'trough' concentration (C0).…”

“…However, this measure does not accurately predict drug exposure, estimated by the area under the time-concentration curve (AUC) (4,6). Since it is generally impractical to perform extensive pharmacokinetic (PK) studies on patients under conditions of normal practice, pharmacokinetic modeling has been used to develop a simple and alternative sparse-sampling method for AUC over the entire 12-h dosage interval (AUC [0][1][2][3][4][5][6][7][8][9][10][11][12]) monitoring in clinical practice (12,13). Studies have suggested a variety of models using time-points throughout the dosing interval for use in clinical practice (14)(15)(16).…”

“…We describe here the significant change in absorption profile and relative absorption which occurs during the first 3 months after renal transplantation; we identify the simplest and most practical sparse-sampling methods for prediction of absorption profile during this time, and demonstrate that the choice of predictors differs importantly when measuring AUC [0][1][2][3][4] or AUC [0][1][2][3][4][5][6][7][8][9][10][11][12]. The feasibility, accuracy, precision and utility of absorption profiling are reported in the companion article.…”

Improved cyclosporine bioavailability in black pediatric liver transplant recipients after administration of the microemulsion formulation

“…A substantial increase in the maximum blood concentration (C max ) of cyclosporine, a decrease in the time to attain this concentration (t max ), and an increase in cyclosporine bioavailability (area under the concentration-versustime curve [AUC]) have all been associated with NL administration. [15][16][17][18] Moreover, intrapatient variability (as determined by the percent coefficient of variation) of cyclosporine AUC has been found to be significantly reduced with NL versus the traditional cyclosporine formulation (SIM). [15][16][17] Thus, the NL formulation provides greater absorption with more consistent and predictable cyclosporine exposure.…”

“…[15][16][17][18] Moreover, intrapatient variability (as determined by the percent coefficient of variation) of cyclosporine AUC has been found to be significantly reduced with NL versus the traditional cyclosporine formulation (SIM). [15][16][17] Thus, the NL formulation provides greater absorption with more consistent and predictable cyclosporine exposure. Pediatric liver transplant recipients are particularly prone to cyclosporine malabsorption because of shortened bowel length and/or increased clearance.…”