The relationship between mannitol pharmacokinetics and changes in serum osmolality were studied in dogs and humans. Four human subjects each received between 0.5 and 0.7 g/kg of mannitol as an i.v. infusion given over 15 min. Intravenous bolus doses of 0.5, 1.0 and 1.5 g/kg were given to each of five animals. Serial determinations of serum osmolality and serum mannitol concentrations were then performed. Mannitol disposition was best described using a biexponential equation and assuming a two-compartment, open model with elimination from the central compartment. For human subjects, the mean (± S.D.) distribution half-life was 2.11 ± 2.67 min and the elimination half-life was 71.15 ± 27.02 min. The volume of distribution was 0.47 ± 0.50 liters/kg and total body clearance was 7.15 ± 10.23 ml.min-1.kg-1. The disposition of mannitol in dogs is similar to that observed in humans. Mannitol clearance was independent of dose whereas the central compartment volume was significantly larger (P<.005) in animals receiving the 1.5-g/kg dose. The volume change is probably due to a rapid, uncompensated shift of water from intracellular to extracellular space. There was a strong positive correlation (r = 0.90) between mannitol concentration and serum osmolality changes. However, neither maximum serum mannitol concentration nor maximum serum osmolality increased proportionately with dose. Only the 1.5-g/kg dose produced a sustained elevation of serum osmolality, confirming that larger doses are more likely to result in prolonged hypertonic dehydration.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1986|