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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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Plasma and blood cell deuterium to protium ratio (D/H) over the 60-min period following ingestion of labeled water (mean ± SD, n = 36). Blood samples were taken at min 0, 5, 10, 15 20, 30 and 60 but for the sake of clarity the data points for plasma and blood cell D/H have been slightly shifted to the left and right, respectively
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Fig1: Plasma and blood cell deuterium to protium ratio (D/H) over the 60-min period following ingestion of labeled water (mean ± SD, n = 36). Blood samples were taken at min 0, 5, 10, 15 20, 30 and 60 but for the sake of clarity the data points for plasma and blood cell D/H have been slightly shifted to the left and right, respectively

Mentions: Background D/H before ingestion of labeled water in the 36 subjects ranged between 147 and 154 ppm and was not significantly different in urine, saliva, plasma or blood cells (149.0 ± 1.0, 149.1 ± 0.8, 148.8 ± 0.9 and 149.1 ± 1.4 ppm, one-way ANOVA for repeated measurements, P = 0.30). Following ingestion of labeled water, plasma and blood cell D/H quickly increased over basal values (Fig. 1). Both plasma and blood cell D/H were significantly above baseline values (see above) beginning at min 5: 192.8 ± 30.6 and 192.2 ± 30.8 ppm, respectively (Student t test for paired data, P < 0.0001); 95% confidence interval around the mean = 148–149 and 182–202 ppm for both plasma and blood cells at baseline and min 5, respectively. Individual D/H values in blood cells were remarkably similar to those observed in plasma (data not shown: mean difference ± SD = 0.8 ± 1.6 ppm, n = 252). Accordingly, the average value and dispersion of blood cell D/H were similar to the corresponding plasma values at all time points during the 60-min observation period [Fig. 1; two-way ANOVA for repeated measures (time × medium): no significant difference between media, P = 0.114]. Average peak plasma and blood cell D/H were reached at min 20, although individual time to peak ranged between min 15 and 60 (Fig. 2).Fig. 1


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)

Plasma and blood cell deuterium to protium ratio (D/H) over the 60-min period following ingestion of labeled water (mean ± SD, n = 36). Blood samples were taken at min 0, 5, 10, 15 20, 30 and 60 but for the sake of clarity the data points for plasma and blood cell D/H have been slightly shifted to the left and right, respectively
© Copyright Policy
Related In: Results  -  Collection

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

Fig1: Plasma and blood cell deuterium to protium ratio (D/H) over the 60-min period following ingestion of labeled water (mean ± SD, n = 36). Blood samples were taken at min 0, 5, 10, 15 20, 30 and 60 but for the sake of clarity the data points for plasma and blood cell D/H have been slightly shifted to the left and right, respectively
Mentions: Background D/H before ingestion of labeled water in the 36 subjects ranged between 147 and 154 ppm and was not significantly different in urine, saliva, plasma or blood cells (149.0 ± 1.0, 149.1 ± 0.8, 148.8 ± 0.9 and 149.1 ± 1.4 ppm, one-way ANOVA for repeated measurements, P = 0.30). Following ingestion of labeled water, plasma and blood cell D/H quickly increased over basal values (Fig. 1). Both plasma and blood cell D/H were significantly above baseline values (see above) beginning at min 5: 192.8 ± 30.6 and 192.2 ± 30.8 ppm, respectively (Student t test for paired data, P < 0.0001); 95% confidence interval around the mean = 148–149 and 182–202 ppm for both plasma and blood cells at baseline and min 5, respectively. Individual D/H values in blood cells were remarkably similar to those observed in plasma (data not shown: mean difference ± SD = 0.8 ± 1.6 ppm, n = 252). Accordingly, the average value and dispersion of blood cell D/H were similar to the corresponding plasma values at all time points during the 60-min observation period [Fig. 1; two-way ANOVA for repeated measures (time × medium): no significant difference between media, P = 0.114]. Average peak plasma and blood cell D/H were reached at min 20, although individual time to peak ranged between min 15 and 60 (Fig. 2).Fig. 1

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