Method for replacing biomarkers of protein kinetics from tissue samples by biomarkers of protein kinetics from body fluids after isotopic labeling in vivo
US-9134319-B2 · Sep 15, 2015 · US
US9737260B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9737260-B2 |
| Application number | US-201615098217-A |
| Country | US |
| Kind code | B2 |
| Filing date | Apr 13, 2016 |
| Priority date | Dec 7, 2011 |
| Publication date | Aug 22, 2017 |
| Grant date | Aug 22, 2017 |
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The present invention is based on the finding that enrichment of D3-creatinine in a urine sample following oral administration of a single defined dose of D3-creatine can be used to calculate total-body creatine pool size and total body skeletal muscle mass in a subject. The invention further encompasses methods for detecting creatinine and D3-creatinine in a single sample. The methods of the invention find use, inter alia, in diagnosing disorders related to skeletal muscle mass, and in screening potential therapeutic agents to determine their effects on muscle mass.
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That which is claimed: 1. A method of determining total body skeletal muscle mass in a subject, comprising: (a) orally administering D 3 -creatine to a subject, wherein the D 3 -creatine dilutes in the total body skeletal muscle pool of creatine and reaches isotopic steady-state in the total body skeletal muscle pool of creatine; (b) obtaining a biological sample comprising creatinine and D 3 -creatinine from the subject, wherein the biological sample is a urine sample; (c) detecting creatinine and D 3 -creatinine in the biological sample by a method selected from the group consisting of HPLC/MS, HPLC/MS/MS, LCMS, LC/MS/MS, and isotope ratio mass spectrometry (IRMS); (d) measuring enrichment ratio of D 3 -creatinine in the biological sample at a time t based on the creatinine and D 3 -creatinine detected in (c); (e) measuring a total amount of urinary D 3 -creatinine from administration of the D 3 -creatine to the time t; (f) determining total-body creatine pool size in the subject by the formula [ Amount of D 3 - creatine dosed ( g ) - Total amount of urinary D 3 - creatine ( o - t ) ( g ) ] enrichment ratio ( t ) = total - body creatine pool size ; and (g) determining total body skeletal muscle mass in the subject based on the formula Total body skeletal muscle mass = ( the total - body creatine pool size creatine concentration in skeletal muscle
involving creatine or creatinine · CPC title
urine · CPC title
for taking urine samples (measuring urological functions A61B5/20; genital receptacles A61F5/451; urinals for bed-ridden persons A61G9/006) · CPC title
Determining body composition · CPC title
Devices for taking samples of blood · CPC title
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