Mannitol
Mannitol, a sweetener. Six-carbon sugar alcohol (hexitol), the reduced form of mannose, non-glycemic and non-cariogenic. Orally it is poorly… IV half-life 1.2 h.
Six-carbon sugar alcohol (hexitol), the reduced form of mannose, non-glycemic and non-cariogenic. Orally it is poorly absorbed — lacking an active intestinal transporter, it crosses the mucosa slowly by passive diffusion, so the bulk reaches the colon where it draws water osmotically (laxative) and is fermented by gut flora to short-chain fatty acids and gas, yielding only ~1.6 kcal/g; the absorbed fraction is largely excreted unchanged in urine, not metabolised by hexokinase. Given intravenously it is a distinct clinical agent: confined to extracellular fluid, freely filtered at the glomerulus and essentially non-reabsorbed, it acts as an osmotic diuretic and raises plasma osmolality to pull water from brain and ocular tissue, lowering intracranial and intraocular pressure before renal clearance largely intact.
ROUTES REORDERED so the dosing default is a solvable route, and the reason is pharmacology rather than presentation: ORAL MANNITOL IS ESSENTIALLY UNABSORBED and acts luminally as an osmotic agent, so there is no systemic curve to render for it. PO stays declared because it is a real use; IV is the route with an exposure. E421 sugar-alcohol bulk sweetener, ~50-60% as sweet as sucrose at ~1.6 kcal/g; JECFA ADI "not specified" and EU-permitted quantum satis, but foods exceeding ~10% polyol must carry a "excessive consumption may produce laxative effects" warning. The IV form (Osmitrol) is a prescription osmotic diuretic, a distinct use from the food additive. IV PK (Cloyd 1986, n=4 humans): apparent Vd ~0.47 L/kg (≈32.9 L/70 kg, high inter-subject variance) and terminal t½ ~71 min (1.19 h) — a 1-compartment approximation of the reported 2-compartment fit (the ~2 min distribution phase is negligible here). PK: THE NOTE CLAIMED A ONE-COMPARTMENT APPROXIMATION THAT DOES NOT CLOSE. All three numbers are verbatim from four human subjects — "the mean ... 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 X min-1 X kg-1" — but the stored volume paired with the stored half-life asserts a clearance of 19.2 L/h against that paper own 30.0, HALF AGAIN TOO SLOW, so the record was not the approximation it said it was. The volume becomes the verbatim clearance over the verbatim rate, and exposure now reproduces the paper. A CAVEAT LARGER THAN THE CORRECTION: this is four subjects and EVERY REPORTED STANDARD DEVIATION EXCEEDS ITS OWN MEAN, so the 1.56-fold gap sits comfortably inside the noise and the fix buys internal coherence rather than accuracy. THE ORAL ROUTE IS DELIBERATELY LEFT WITHOUT PARAMETERS: it is declared with a food-additive dose and no pharmacokinetics, so it yields no curve at all — and here that is CORRECT rather than broken, because oral mannitol is minimally absorbed and acts osmotically in the gut lumen, which is also why the laxative warning exists.
Pharmacokinetics
- IV — t½ 1.2 h · F 100% · Vd 51.4 L
Sources: PMID:3080582