A comparison of the pharmacokinetics of tacrolimus and microemulsified cyclosporin in paediatric renal transplant recipients

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Abstract

Objective: Our objective was to identify common factors that determine the dose of tacrolimus and microemulsified cyclosporin in paediatric renal transplant recipients. Methods: The concentration profiles of tacrolimus and cyclosporin in blood were determined in 68 children who had received a renal transplant. To avoid disruption of therapy, measurements were made at 2-h intervals over an 8-h period during normal dosing regimens. Direct comparisons of the two drugs were made in 14 of the subjects who were switched from cyclosporin to tacrolimus. Results: The ratio of peak to trough levels for tacrolimus was approximately twofold compared with over threefold for cyclosporin. Area under the curve (AUC) for tacrolimus remained relatively constant in each 2-h period of the dosage interval compared with the AUC for cyclosporin, which varied by over twofold in the same time period. In the 14 subjects who received both drugs, there was a poor correlation between C 2/C0, C2, t1/2 and AUC for tacrolimus and cyclosporin in the same individual. In a multivariate analysis, there were no significant associations for tacrolimus concentrations, AUC or C2/C0 with age, gender, calcium-channel blocker, quinolone or statin. For cyclosporin, there was some association for AUC with gender and quinolone use and a weak association with calcium-channel blocker or statin use. Conclusions: Tacrolimus and microemulsified cyclosporin display a wide intra- and inter-individual variation in pharmacokinetic properties in young subjects. In the case of absorption represented by the peak-trough ratios, the values for tacrolimus are significantly less than those obtained with cyclosporin. The pharmacokinetic parameters obtained for one of these agents is not predictive for the behaviour of the other in young renal transplant recipients.

Original languageEnglish
Pages (from-to)421-426
Number of pages6
JournalEuropean Journal of Clinical Pharmacology
Volume60
Issue number6
DOIs
Publication statusPublished - Aug 2004

ASJC Scopus Subject Areas

  • Pharmacology
  • Pharmacology (medical)

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