Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth.
Level 5 - mechanism / opinion, no new human data
Animal pharmacokinetic study and computational modeling (no human data)
PubMed 29518030 · doi:10.3390/pharmaceutics10010031
What was done
Rats were orally administered 13C-labeled creatine monohydrate (CM) at either a low dose (10 mg/kg) or a high dose (70 mg/kg). Blood samples were collected at various time points, and muscle and brain tissues were harvested at the end of the study. Plasma and tissue concentrations of 13C-labeled creatine were quantified via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Physiologically based pharmacokinetic (PBPK) models were constructed using GastroPlus to predict and compare plasma concentration-time profiles and bioavailability of creatine hydrochloride (CHCL) versus CM.
What was found
Absolute oral bioavailability of CM in rats was 53% at the 10 mg/kg dose and 16% at the 70 mg/kg dose. PBPK simulations for a 70 mg/kg dose predicted a Cmax of around 35 μg/mL for CHCL versus 14 μg/mL for CM, with a predicted bioavailability of 66% for CHCL compared to 17% for CM.
Why it matters
This study indicates that creatine monohydrate bioavailability is incomplete and dose-dependent in rats, suggesting that alternative formulations with higher aqueous solubility may improve oral absorption.
Limits
The study was conducted entirely in an animal model and computational simulations, which may not directly translate to human pharmacokinetics. The abstract does not report the total sample size (n), variance around the estimates, or numeric values for tissue concentrations.
Cited by
- contradicts The bioavailability of creatine monohydrate is nearly 100%.