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Pharmaceutics 2018, 10(1), 31; https://doi.org/10.3390/pharmaceutics10010031

Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth

1
Department of Pharmacology and Therapeutics, The Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3J7, Canada
2
Pharmaceutical Analysis Laboratory, College of Pharmacy, The Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
3
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6125, USA
*
Author to whom correspondence should be addressed.
Received: 8 November 2017 / Revised: 13 February 2018 / Accepted: 27 February 2018 / Published: 8 March 2018
(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)
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Abstract

Creatine is an ergogenic compound used by athletes to enhance performance. Supplementation with creatine monohydrate (CM) has been suggested for musculoskeletal and neurological disorders. Until now, little is known about its pharmacokinetic profile. Our objective was to determine the oral bioavailability of CM and the influence of dose on oral absorption. Rats were dosed orally with low dose (10 mg/kg) or high dose (70 mg/kg) 13C-labeled CM. Blood samples were removed at various time points. Muscle and brain tissue were collected at the conclusion of the study. Plasma and tissue levels of 13C-labeled creatine were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Physiologically based pharmacokinetic (PBPK) models of CM were built using GastroPlus™. These models were used to predict the plasma concentration–time profiles of creatine hydrochloride (CHCL), which has improved aqueous solubility compared to CM. Absolute oral bioavailability for low dose CM was 53% while high dose CM was only 16%. The simulated Cmax of 70 mg/kg CHCL was around 35 μg/mL compared to 14 μg/mL for CM with a predicted oral bioavailability of 66% with CHCL compared to 17% with CM. Our results suggest that the oral bioavailability of CM is less than complete and subject to dose and that further examination of improved dosage formulations of creatine is warranted. View Full-Text
Keywords: creatine monohydrate; pharmacokinetics; oral bioavailability; LC-MS/MS; physiology-based pharmacokinetic modeling creatine monohydrate; pharmacokinetics; oral bioavailability; LC-MS/MS; physiology-based pharmacokinetic modeling
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Alraddadi, E.A.; Lillico, R.; Vennerstrom, J.L.; Lakowski, T.M.; Miller, D.W. Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth. Pharmaceutics 2018, 10, 31.

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