title: Single- and multiple-dose pharmacokinetics of oral creatine.
abstract: 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, tmax was 1.9 +/- 0.88 hours, and Cmax = 102.1 +/- 11.2 mg h L-1. At steady-state, CL/F decreased to 0.12 +/- 0.016 L h-1 kg-1, tmax did not change, and Cmax increased to 162.2 +/- 30.0 mg L-1. Penetration (AUCMUSCLE/AUCPLASMA) 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.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Persky
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.forename: Maria
authors.initials: M
authors.lastname: Grant
authors.forename: Gayle A
authors.initials: GA
authors.lastname: Brazeau
authors.forename: Günther
authors.initials: G
authors.lastname: Hochhaus
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D003401:Creatine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D008297:Male; D017551:Microdialysis; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D003401:Creatine