Aspirin itself is an acid with a pKa of 3.5 and is relatively insoluble in water, while its sodium or calcium salts have enhanced solubility. Aspirin and related sali-cylates are rapidly absorbed upon oral administration, with most absorption occurring in the small intestine. The pH of the stomach, a secondary site of drug absorption, along with the gastric emptying time of the stomach, determines the rate of absorption of the drug. Thus, food, which alters gastric emptying time and possibly the pH of the stomach, will alter absorption of the drug. Buffering of the drug decreases irritation in the stomach, increases drug solubility, and therefore may increase the rapidity of absorption. Enteric-coated aspirin tablets have a variable rate of dissolution depending on the preparation but are somewhat useful for prevention of stomach ulceration and gastric distress. Absorption of aspirin from rectal suppositories is slower and more variable than from oral administration. The peak plasma concentration of aspirin occurs 1 to 2 hours following oral administration. Aspirin is immediately hydrolyzed by various esterases in the stomach and in the liver to acetate and salicylic acid. Salicylic acid is glucuronidated, conjugated to glycine to form salicyluric acid (the major metabolic pathway), oxidized to gentisic acid (a minor metabolic pathway), or remains free as salicylic acid, which is secreted in the proximal tubule of the kidney. Diflunisal (Dolobid) differs from other salicylates in that it is not metabolized to salicylic acid but is rapidly glucuronidated. The conjugated metabolites of salicylates are inactive.

Salicylic acid is highly plasma protein bound, an effect that alters the pharmacokinetics of other drugs taken in combination with aspirin. Salicylates passively diffuse to all tissues, including breast milk, fetal tissues, and the CNS. They tend to accumulate, since increases in dose decrease renal clearance and prolong the half-life of the drug. Clearance at high doses (>2-4 g/day) is via zero order kinetics, and the half-life can approach 15 hours. At lower doses (600-1000 mg/day), clearance depends on the concentration of glucuronide or glycine available for conjugation and is a first-order process (half-life of approximately 3-6 hours). However, renal clearance is highly dependent on the pH of the urine; the higher the pH of the urine, the greater the clearance of the drug. Alkalinization of the urine is used to increase clearance of the salicylates in the case of toxicity or overdose.

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Peripheral Neuropathy Natural Treatment Options

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