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Single- and Multiple-Dose Pharmacokinetics of Oral Creatine

From the Department of Pharmaceutics, College of Pharmacy (Dr. Persky, Dr. Müller, Dr. Derendorf, Dr. Hochhaus) and Department of Pharmacology, College of Medicine (Dr. Grant), University of Florida, Gainesville, Florida; Vienna University School of Medicine, Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Vienna General Hospital, Vienna, Austria (Dr. Müller); and Departments of Pharmacy Practice and Pharmaceutical Science, School of Pharmacy Practice and Pharmaceutical Science, University of Buffalo, State University of New York, Amherst, New York (Dr. Brazeau). Dr. Persky's current affiliation is the Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill.

Supplementation with exogenous creatine (Cr) has shown physiological benefits in humans, but little is known about the pharmacokinetics of Cr in humans. Six healthy males completed an open-label study consisting of a full pharmacokinetic analysis following a single oral dose of Cr monohydrate (71 mg kg^-1) and at steady-state after 6 days of Cr administration (71 mg kg^-1 qid). After the single oral dose, the clearance (CL/F) was 0.20 ± 0.066 L h^-1 kg^-1,t_max was 1.9 ± 0.88 hours, and C_max = 102.1 ± 11.2 mg h L^-1. At steady-state, CL/F decreased to 0.12 ± 0.016 L h^-1 kg^-1,t_max did not change, and C_max increased to 162.2 ± 30.0 mg L^-1. Penetration (AUC_MUSCLE/AUC_PLASMA) of Cr into the interstitial muscle space, as determined by microdialysis, was 0.47 ± 0.09 and 0.37 ± 0.27 for the single dose and at steady-state, respectively. Plasma and muscle data were simultaneously fitted with a model incorporating a saturable absorption and first-order elimination process. In conclusion, repeated dosing of Cr caused a reduction in clearance that could result from saturation of the skeletal muscle pool of Cr.

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