Cyclosporine -- Drug Interactions and the Influence of Patient Age

Jennifer Lill, Larry A. Bauer, John R. Horn, and Philip D. Hansten


Am J Health Syst Pharm. 2000;57(17) 

In This Article


Hospitalized and ambulatory care patients receiving cyclosporine therapy and older than 18 years were identified from clinical laboratory and toxicology reports. The medical records of these patients were reviewed to acquire the following information: age, sex, weight, cyclosporine dosage, dosage form, reason for and duration of cyclosporine use, times of cyclosporine administration, blood cyclosporine concentrations immediately before the next dose (trough concentrations), concurrent medications (including dosage and administration route), and pertinent laboratory test values, including aspartate transaminase, alanine transaminase, bilirubin, serum creatinine, and serum albumin concentrations. Subjects taking either the conventional or the emulsion formulation of cyclosporine were included in the study unless their dosage form was switched during the data collection period. Before the study began, the human subjects committee for the University of Washington Medical Center approved the use of patient medical records at this institution to collect data pertinent to achieving the study's objectives.

One-compartment models for i.v. and oral administration were used to fit cyclosporine concentration data to population pharmacokinetic and statistical models. This was achieved with nonlinear mixed-effect modeling software (NONMEM, version 5.0, University of California, SanFrancisco). Data for i.v. administration were used to determine the mean bioavailability of cyclosporine in the study population.

Baseline clearance of cyclosporine was determined with a regression model that excluded all potential covariates. Potential covariates were then added sequentially to the "baseline" regression model. Covariates that significantly improved (c 2 = 3.814, p < 0.05) the NONMEM objective function were used to build the final model with the forward-inclusion, backward-elimination approach.[14] Interindividual variability for cyclosporine clearance, volume of distribution, and bioavailability, as well as residual intrapatient variability, was statistically modeled by using the constant coefficient of variation method.

The mean number of medications taken by patients ≥60 years of age was compared with the mean number taken by patients <60 years of age. Values were compared by using Student's t test (a = 0.05) (SPSS for Windows, version 9.0, SPSS, Inc., Chicago, IL). Whole-blood cyclosporine concentrations were determined by using a high-performance liquid chromatographic assay with an interday coefficient of variation of <10%.15


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