Pharmacokinetic analysis of absorption, distribution and disappearance of ingested water labeled with D ₂O in humans

Abstract

The kinetic parameters of absorption and distribution of ingested water (300 ml labeled with D ₂O; 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 ₂O 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.