Comparison of the pharmacokinetics of tacrolimus and cyclosporine at equivalent molecular doses

Transplant Proc. 2003 Jun;35(4):1314-8. doi: 10.1016/s0041-1345(03)00481-0.


Even though calcineurin inhibitors, namely Tacrolimus (FK) and Cyclosporine (CsA) share similar physicochemical properties and a common mechanism of action, their pharmacokinetics (pk) are different and unpredictable. Both drugs are metabolized by cytochrome P450-3A4 isoforms in the liver and in the mucosa of the upper gastrointestinal tract. FK in clinical practice is given in doses up to 50-fold lower than those of CsA due to its greater potency. It is often assumed that the diverse dosing contributes to the observed pharmacokinetic differences between the two drugs. The objective of the present study was to compare single-dose pk profiles of the two drugs, following oral and intravenous administration, on the basis of equivalent molecular dosing, thus ruling out the quantitative factor. Five healthy volunteers and 14 dialysis patients (7 hemodialysis, 7 peritoneal dialysis) were included in the study. Comparing the pharmacokinetic parameters obtained from the drugs, it appeared that cyclosporine has an greater primary volume of distribution and clearance rate compared to tacrolimus. No other statistically significant differences were observed regarding bioavailability, absorption rate, or elimination rate. The only significant correlation between the pk values of the drugs was in primary volume of distribution. We conclude that even at equivalent molecular doses the pk of each drug remains unique and unpredictable. Furthermore our data fail to reveal significant correlations between the bioavailability, clearance, absorption, and elimination rates of the two drugs.

Publication types

  • Comparative Study

MeSH terms

  • Biotransformation
  • Cyclosporine / pharmacokinetics*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Gastric Mucosa / enzymology
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Intestinal Mucosa / enzymology
  • Liver / enzymology
  • Peritoneal Dialysis
  • Reference Values
  • Renal Dialysis
  • Tacrolimus / pharmacokinetics*
  • Waiting Lists


  • Immunosuppressive Agents
  • Cyclosporine
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Tacrolimus