Source: FDA, National Drug Code (US) Revision Year: 2018
Mannitol, when administered intravenously, exerts its osmotic diuretic effect as a solute of relatively small molecular size being largely confined to the extracellular space. Mannitol hinders tubular reabsorption of water and enhances excretion of sodium and chloride by elevating the osmolarity of the glomerular filtrate.
This increase in extracellular osmolarity affected by the intravenous administration of mannitol will induce the movement of intracellular water to the extracellular and vascular spaces. This action underlies the role of mannitol in reducing intracranial pressure, intracranial edema, and intraocular pressure.
Mannitol distributes largely in the extracellular space in 20 to 40 minutes after intravenous administration. The volume of distribution of mannitol is approximately 17 L in adults.
In subjects with normal renal function, the total clearance is 87 to 109 mL/min. The elimination half-life of mannitol is 0.5 to 2.5 hours.
Only relatively small amount of the dose administered is metabolized after intravenous administration of mannitol to healthy subjects.
Mannitol is eliminated primarily via the kidneys in unchanged form. Mannitol is filtered by the glomeruli, exhibits less than 10% of tubular reabsorption, and is not secreted by tubular cells. Following intravenous administration, approximately 80% of an administered dose of mannitol is estimated to be excreted in the urine in three hours with lesser amounts thereafter.
In patients with renal impairment, the elimination half-life of mannitol is prolonged. In a published study, in patients with renal impairment including acute renal failure and end stage renal failure, the elimination half-life of mannitol was estimated at about 36 hours, based on serum osmolarity. In patients with renal impairment on dialysis, the elimination half-life of mannitol was reduced to 6 and 21 hours during hemodialysis and peritoneal dialysis, respectively [see Use in Specific Populations (8.6), Overdosage (10)].
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