Clinical Pharmacokinetics

, Volume 42, Issue 6, pp 557–574 | Cite as

Pharmacokinetics of the Dietary Supplement Creatine

  • Adam M. Persky
  • Gayle A. Brazeau
  • Günther Hochhaus
Review Article


Creatine is a nonessential dietary component that, when supplemented in the diet, has shown physiological benefits in athletes, in animal-based models of disease and in patients with various muscle, neurological and neuromuscular disease. The clinical relevance of creatine supplementation is based primarily on its role in ATP generation, and cells may be able to better handle rapidly changing energy demands with supplementation.

Although the pharmacological outcome measures of creatine have been investigated, the behaviour of creatine in the blood and muscle is still not fully understood. Creatine is most probably actively absorbed from the gastrointestinal tract in a similar way to amino acids and peptides. The distribution of creatine throughout the body is largely determined by the presence of creatine transporters. These transporters not only serve to distribute creatine but serve as a clearance mechanism because of creatine ‘trapping’ by skeletal muscle. Besides the pseudo-irreversible uptake by skeletal muscle, creatine clearance also depends on renal elimination and degradation to creatinine.

Evidence suggests that creatine pharmacokinetics are nonlinear with respect to dose size and frequency. Skeletal muscle, the largest depot of creatine, has a finite capacity to store creatine. As such, when these stores are saturated, both volume of distribution and clearance can decrease, thus leading to complex pharmacokinetic situations. Additionally, other dietary components such as caffeine and carbohydrate can potentially affect pharmacokinetics by their influence on the creatine transporter. Disease and age may also affect the pharmacokinetics, but more information is needed.

Overall, there are very limited pharmacokinetic data available for creatine, and further studies are needed to define absorption characteristics, clearance kinetics and the effect of multiple doses. Additionally, the relationship between plasma creatine and muscle creatine needs to be elucidated to optimise administration regimens.


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Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Adam M. Persky
    • 1
  • Gayle A. Brazeau
    • 2
  • Günther Hochhaus
    • 1
  1. 1.Department of Pharmaceutics, College of PharmacyUniversity of FloridaGainesvilleUSA
  2. 2.Department of Pharmacy Practice and PharmaceuticsState University of New York at BuffaloAmherstUSA
  3. 3.Division of Drug Delivery and DispositionUniversity of North CarolinaChapel HillUSA

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