Single-dose oral guanidinoacetic acid exhibits dose-dependent pharmacokinetics in healthy volunteers

被引:8
|
作者
Ostojic, Sergej M. [1 ,2 ]
Vojvodic-Ostojic, Aleksandra [3 ]
机构
[1] Ctr Hlth Exercise & Sport Sci, Exercise Physiol Lab, Belgrade 11000, Serbia
[2] Univ Novi Sad, Fac Sport & Phys Educ, Dept Biomed Sci, Novi Sad 21000, Serbia
[3] Univ Belgrade, Fac Technol & Met, Dept Environm Engn, Belgrade 11000, Serbia
关键词
Guanidinoacetic acid; Pharmacokinetics; Area under the curve; Elimination half-life; Clearance; SERUM CREATINE; HOMOCYSTEINE; RAT; METABOLISM; PROFILES;
D O I
10.1016/j.nutres.2014.12.010
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Guanidinoacetic acid (GAA), the natural precursor of creatine, has potential as a dietary supplement for human nutrition, yet no data are available regarding its dose-dependent pharmacokinetic (PK) behavior. We hypothesized that a single dose of orally administered GAA exhibited dose-dependent PK behavior in healthy volunteers. Forty-eight young adults were enrolled in a randomized, placebo-controlled, double-blind, parallel-group trial to receive single oral doses of GAA (1.2, 2.4, and 4.8 g) or a placebo. Pharmacokinetic metrics for plasma GAA and creatine were assessed immediately before (0 hours) and at 1, 2, 4, 6, 8, 12, and 24 hours after GAA ingestion. The lag time appeared to be similar after the bolus ingestion of GAA (0.14 +/- 0.17 hours for low-dose GAA, 0.31 +/- 0.18 hours for medium-dose GAA, and 0.38 +/- 0.32 hours for high-dose GAA; P = .05). An increase in the area under the concentration-time curve for plasma GAA was found for the dose range tested, with 2.4- and 9.3-fold increases in the area under the concentration-time curve for every 2-fold increase in the GAA dose (P < .0001). No differences were found for elimination half-time between the low-dose and medium-dose groups (<1.75 hours), whereas the elimination half-time was significantly longer (>2.1 hours) for the high-dose GAA regimen (P = .001). The volume of distribution was affected by the dosage of GAA applied (102.6 +/- 17.3 L for low-dose GAA, 97.5 +/- 15.7 L for medium-dose GAA, and 61.1 +/- 12.7 L for high-dose GAA; P < .0001). Ingestion of GAA elevated plasma,creatine by 80%, 116%, and 293% compared with the placebo for the 1.2, 2.4, and 4.8 g doses, respectively (P < .0001). Guanidinoacetic acid single-dose PK metrics were nonlinear with respect to dose size. Across the dose range of 1.2 to 4.8 g, systemic exposure to GAA increased in a greater than dose-proportional manner. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:198 / 205
页数:8
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