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Pharmacokinetic analysis of absorption, distribution and disappearance of ingested water labeled with D₂O in humans.

Péronnet F, Mignault D, du Souich P, Vergne S, Le Bellego L, Jimenez L, Rabasa-Lhoret R - Eur. J. Appl. Physiol. (2011)

Bottom Line: Compared with the volume and turnover of the BWP computed with the slope-intercept method (60.7 ± 4.1% body mass or 72.7 ± 3.2% lean body mass; turnover 4.58 ± 0.80 l day(-1): i.e., complete renewal in ~50 days; n = 36), the values were accurately estimated with the N-CM and 1-CM and were slightly overestimated and underestimated, respectively, with the 2-CM (~7-8% difference, significant for water clearance only).The 2-CM showed that in 42% of the subjects, ingested water quickly distributed within a central compartment before diffusing with a very short half-life (12.5 ± 4.3 min) to a peripheral compartment (18.5 ± 4.3 and 31.6 ± 6.4 L, respectively), which were in complete equilibrium within ~90 min.Pharmacokinetic analyses of water labeled with D(2)O can help describe water absorption and distribution, for which there is no well defined reference method and value; depending on the characteristics of the subjects and the drinks, and of environmental conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Kinesiology, Université de Montréal, PO Box 6128, Centre-Ville, Montreal, QC, H3C 3J7, Canada. Francois.peronnet@umontreal.ca

ABSTRACT
The kinetic parameters of absorption and distribution of ingested water (300 ml labeled with D(2)O; osmolality <20 mOsm kg(-1)) in the body water pool (BWP) and of its disappearance from this pool were estimated in 36 subjects from changes in plasma or urine deuterium to protium ratio (D/H) over 10 days using one- and two-compartment and a non-compartmental pharmacokinetic models (1-CM, 2-CM and N-CM which applied well to 58, 42 and 100% of the subjects, respectively). Compared with the volume and turnover of the BWP computed with the slope-intercept method (60.7 ± 4.1% body mass or 72.7 ± 3.2% lean body mass; turnover 4.58 ± 0.80 l day(-1): i.e., complete renewal in ~50 days; n = 36), the values were accurately estimated with the N-CM and 1-CM and were slightly overestimated and underestimated, respectively, with the 2-CM (~7-8% difference, significant for water clearance only). Ingested water appeared in plasma and blood cells within 5 min and the half-life of absorption (~11-13 min) indicates a complete absorption within ~75-120 min. The 2-CM showed that in 42% of the subjects, ingested water quickly distributed within a central compartment before diffusing with a very short half-life (12.5 ± 4.3 min) to a peripheral compartment (18.5 ± 4.3 and 31.6 ± 6.4 L, respectively), which were in complete equilibrium within ~90 min. Pharmacokinetic analyses of water labeled with D(2)O can help describe water absorption and distribution, for which there is no well defined reference method and value; depending on the characteristics of the subjects and the drinks, and of environmental conditions.

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Mean kinetic parameters within a two compartment model and volume of the central (V1) and peripheral compartment (V2) (mean ± SD). ka rate constant of water absorption in the central compartment; k12 and k21 rate constant of water transfer between V1 and V2, and V2 and V1; kel rate constant of elimination from the central and peripheral compartments (kel1 and kel2, respectively)
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Fig3: Mean kinetic parameters within a two compartment model and volume of the central (V1) and peripheral compartment (V2) (mean ± SD). ka rate constant of water absorption in the central compartment; k12 and k21 rate constant of water transfer between V1 and V2, and V2 and V1; kel rate constant of elimination from the central and peripheral compartments (kel1 and kel2, respectively)

Mentions: As shown in Fig. 3, for group 1, the volume of the central compartment computed using the 2-CM [18.5 ± 4.3 l, corresponding to 37 ± 10% of the total BWP and including the blood (~6 l in 76.9-kg subjects) but also a portion of extra-vascular space] was smaller than that of the peripheral compartment (31.6 ± 6.4 l or 63 ± 10% of the BWP). The microconstants depicted in Fig. 3 show that the rate constant of absorption was much greater than the inter-compartmental transfer constants and the elimination rate constant. The half-life of water distribution between the central and peripheral compartment (td½) was estimated to be 12.5 ± 4.3 min, indicating that ~90 min after ingestion, labeled water was almost evenly distributed within the entire BWP (>99% of the pool).Fig. 3


Pharmacokinetic analysis of absorption, distribution and disappearance of ingested water labeled with D₂O in humans.

Péronnet F, Mignault D, du Souich P, Vergne S, Le Bellego L, Jimenez L, Rabasa-Lhoret R - Eur. J. Appl. Physiol. (2011)

Mean kinetic parameters within a two compartment model and volume of the central (V1) and peripheral compartment (V2) (mean ± SD). ka rate constant of water absorption in the central compartment; k12 and k21 rate constant of water transfer between V1 and V2, and V2 and V1; kel rate constant of elimination from the central and peripheral compartments (kel1 and kel2, respectively)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351614&req=5

Fig3: Mean kinetic parameters within a two compartment model and volume of the central (V1) and peripheral compartment (V2) (mean ± SD). ka rate constant of water absorption in the central compartment; k12 and k21 rate constant of water transfer between V1 and V2, and V2 and V1; kel rate constant of elimination from the central and peripheral compartments (kel1 and kel2, respectively)
Mentions: As shown in Fig. 3, for group 1, the volume of the central compartment computed using the 2-CM [18.5 ± 4.3 l, corresponding to 37 ± 10% of the total BWP and including the blood (~6 l in 76.9-kg subjects) but also a portion of extra-vascular space] was smaller than that of the peripheral compartment (31.6 ± 6.4 l or 63 ± 10% of the BWP). The microconstants depicted in Fig. 3 show that the rate constant of absorption was much greater than the inter-compartmental transfer constants and the elimination rate constant. The half-life of water distribution between the central and peripheral compartment (td½) was estimated to be 12.5 ± 4.3 min, indicating that ~90 min after ingestion, labeled water was almost evenly distributed within the entire BWP (>99% of the pool).Fig. 3

Bottom Line: Compared with the volume and turnover of the BWP computed with the slope-intercept method (60.7 ± 4.1% body mass or 72.7 ± 3.2% lean body mass; turnover 4.58 ± 0.80 l day(-1): i.e., complete renewal in ~50 days; n = 36), the values were accurately estimated with the N-CM and 1-CM and were slightly overestimated and underestimated, respectively, with the 2-CM (~7-8% difference, significant for water clearance only).The 2-CM showed that in 42% of the subjects, ingested water quickly distributed within a central compartment before diffusing with a very short half-life (12.5 ± 4.3 min) to a peripheral compartment (18.5 ± 4.3 and 31.6 ± 6.4 L, respectively), which were in complete equilibrium within ~90 min.Pharmacokinetic analyses of water labeled with D(2)O can help describe water absorption and distribution, for which there is no well defined reference method and value; depending on the characteristics of the subjects and the drinks, and of environmental conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Kinesiology, Université de Montréal, PO Box 6128, Centre-Ville, Montreal, QC, H3C 3J7, Canada. Francois.peronnet@umontreal.ca

ABSTRACT
The kinetic parameters of absorption and distribution of ingested water (300 ml labeled with D(2)O; osmolality <20 mOsm kg(-1)) in the body water pool (BWP) and of its disappearance from this pool were estimated in 36 subjects from changes in plasma or urine deuterium to protium ratio (D/H) over 10 days using one- and two-compartment and a non-compartmental pharmacokinetic models (1-CM, 2-CM and N-CM which applied well to 58, 42 and 100% of the subjects, respectively). Compared with the volume and turnover of the BWP computed with the slope-intercept method (60.7 ± 4.1% body mass or 72.7 ± 3.2% lean body mass; turnover 4.58 ± 0.80 l day(-1): i.e., complete renewal in ~50 days; n = 36), the values were accurately estimated with the N-CM and 1-CM and were slightly overestimated and underestimated, respectively, with the 2-CM (~7-8% difference, significant for water clearance only). Ingested water appeared in plasma and blood cells within 5 min and the half-life of absorption (~11-13 min) indicates a complete absorption within ~75-120 min. The 2-CM showed that in 42% of the subjects, ingested water quickly distributed within a central compartment before diffusing with a very short half-life (12.5 ± 4.3 min) to a peripheral compartment (18.5 ± 4.3 and 31.6 ± 6.4 L, respectively), which were in complete equilibrium within ~90 min. Pharmacokinetic analyses of water labeled with D(2)O can help describe water absorption and distribution, for which there is no well defined reference method and value; depending on the characteristics of the subjects and the drinks, and of environmental conditions.

Show MeSH