Metformin elimination

Mechanism uncertain. Metformin does not undergo hepatic metabolism. Renal tubular secretion is the major route of metformin elimination. Aminoglycosides are also principally excreted via the kidney, and nephrotoxicity is an important side-effect Watch and monitor for hypoglycaemia, and warn patients about it - For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

Oral formulations of metformin are rapidly and completely absorbed. The agent is poorly bound to plasma proteins its duration of action is determined exclusively by renal elimination. Higher concentrations of metformin than in most tissues are found in the intestinal mucosa, giving tise to common side effects (irritation, diarrhoea etc.). 

Metabolism/Excretion- Metformin is excreted unchanged in the urine and does not undergo hepatic metabolism or biliary excretion. Tubular secretion is the major route of elimination. The elimination half-life is approximately 17.6 hours. 

Drugs that may be affected by trospium include those eliminated by active tubular secretion (eg, digoxin, procainamide, pancuronium, morphine, vancomycin, metformin, and tenofovir). 

Most (70-90%) of a dose of metformin is eliminated via the kidneys with a half-life of 9 hours (6). In contrast, phenformin is mostly eliminated by metabolism its half-life is about 11 hours (7). 

The results of hemodialysis in biguanide-induced lactic acidosis are variable. Metformin and buformin are dialy-sable, but phenformin is poorly eliminated. Successful continuous venovenous hemofiltration has been reported (81). 

METFORMIN NS AIDS Possibility oft plasma levels of metformin if there is renal impairment due to NSAIDs. Phenylbutazone is likely to i renal elimination of metformin and t plasma levels. 

Metformin achieves a 23% lower mean HbAi than placebo (Dornan etal., 1991). Unlike sulphonylureas, it is not bound to plasma proteins (no drug interactions), is not metabolized and is eliminated rapidly by the kidney (Bailey, 1992). 

Treatment with biguanides should begin with a small dose of medication and a progressive build-up over a 1-2-week period (Asmal and Marble, 1984). As far as metformin is concerned, its elimination half-life requires a dosage interval of about 8 h or more (three times or twice a day) which will not induce accumulation when renal function is normal (Pentikainen et al., 1979). 

Metformin has an absolute oral bioavailability of about 50-60% of the dose after oral application of a single dose. Deconvolution analysis showed that after a short lag-time, the available remainder of the oral dose was absorbed at an exponential rate over about 6 h (Tucker et al., 1981). The bioavailability of phenformin seems to be more variable but also in the range of about 50% (Beckmann, 1968 Travis and Sayers, 1970). In general, absorption of biguanides is slower than their elimination, hence the plasma levels follow flip-flop kinetics (Pentikainen et al., 1979). 

Metformin is slowly and incompletely absorbed and rapidly eliminated without hepatic metabolism. This pharmacokinetic profile may make drug accumulation and lactic acidosis less likely to occur with metformin than with other biguanides. Sales of the longer-acting biguanide phenformin (10), for instance, which is metabolized in the liver by aromatic... 

When estimating creatinine clearance in the elderly using the Cockcroft and Gault equation, some clinicians choose to round the value up to 1 if the patient s serum creatinine concentration is less than 1. Rounding the serum creatinine concentration may provide an underestimation of creatinine clearance and result in improper dose adjustment of renally eliminated medications. It is important to realize that the equation is merely an estimate, and attempts should be made to determine creatinine clearance accurately with certain medications (e.g., metformin). 

Pharmacokinetics. Metformin has approximately 50% to 60% oral bioavailability, low lipid solubility, and a volume of distribution that approximates body water. Metformin is not metabolized and does not bind to plasma proteins. Metformin is eliminated by renal tubular secretion and glomerular filtration. The average half-life of metformin is 6 hours, though pharmacodynamically, metformin s an-tihyperglycemic effects last >24 hours. 

Drugs that make the urine alkaline (e.g. sodium bicarbonate, carbonic anhydrase inhibitors) will reduce the elimination of memantine. Memantine should be used with caution with other NMDA antagonists, such as amantadine, ketamine and dextromethorphan, or concurrent use should be avoided, because of the theoretical increased risk of adverse effects. Memantine is predicted to interact with other drugs eliminated by the same renal secretion mechanism, but no important interaction was seen with glibenclamide, hydrochlorothiazide, metformin or triamterene. 

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