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

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.