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Among the organic acids normally found Post Date: Sun, 12 Oct 2008 2:36:18 +0000 The effect of probenecid on the disposition of a number of diagnostic and therapeutic agents in the body is well established. The physician should be alert to the need to modify the dosage of such drugs when they are administered during probenecid ther-apy.Among the organic acids normally found in plasma, several have been shown to be transported by the renal tubule. Autor of the post: Undefined Absorption, Fate, and Excretion Post Date: Sun, 12 Oct 2008 2:18:26 +0000 The transport of some of these, for example, pantothenic acid, is known to be inhib-ited by probenecid. However, no clinical evidence of side effects due to changes in the excretion of essential solutes has been reported.Absorption, Fate, and Excretion. Autor of the post: Undefined The rate of decline Post Date: Sun, 12 Oct 2008 1:58:47 +0000 Pro-benecid is completely absorbed after oral administration. Peak plasma concentrations are reached in 2 to 4 hours. The rate of decline of plasma levels is rather variable. Autor of the post: Undefined The small unbound portion gains Post Date: Sun, 12 Oct 2008 1:45:48 +0000 The half-life of the drug in the plasma of most patients is between 6 and 12 hours. Between 85 and 95% of the drug is bound to plasma protein, largely to albumin. The small unbound portion gains access to the glomerular filtrate; a much larger portion is actively secreted by the proximal tubule. Autor of the post: Undefined It is also hydroxylated Post Date: Sun, 12 Oct 2008 1:26:06 +0000 In spite of its low pKa (3,4), the high lipid solu-bility of the undissociated form results in virtually complete absorption by back diffu-sion unless the urine is markedly alkaline, in which case amounts well in excess of the filtered load may be excreted. A small amount of probenecid glucuronide appears in the urine. It is also hydroxylated to me-tabolites that retain their carboxyl function and have uricosuric activity. Autor of the post: Undefined The free acid is insoluble Post Date: Sun, 12 Oct 2008 1:13:24 +0000 (For details, see Dayton et al, 1963; Israeli et al, Y)12)Preparations and Dosage. Probenecid, USP (BENEMID), is a white crystalline, odorless powder. The free acid is insoluble in water, but the sodium salt is freely soluble. Autor of the post: Undefined To block effectively the renal Post Date: Sun, 12 Oct 2008 0:55:00 +0000 The compound is marketed as oral tablets (500 mg). The dosage schedule depends upon the objectives of therapy. To block effectively the renal excretion of penicillin, a total daily dose of 2 g is employed in adults. Autor of the post: Undefined In the treatment of chronic Post Date: Sun, 12 Oct 2008 0:42:52 +0000 This is administered in four divided doses. The total daily dose for children is from 10 to 25 mg/kg of body weight. In the treatment of chronic gout, a single daily dose of 250 mg is given for 1 week, following which 500 mg is administered twice daily. Autor of the post: Undefined The oral administration of probenecid Post Date: Sun, 12 Oct 2008 0:23:36 +0000 In some patients it may be necessary to increase the daily dose gradually to a maximum of 2 g, given in four divided portions.Adjunct in Penicillin Therapy. The oral administration of probenecid in conjunction with penicillin G given by any route results in higher and more prolonged plasma con-centrations of the antibiotic than when peni-cillin is given alone. Autor of the post: Undefined Probenecid also retards the renal excretion Post Date: Sun, 12 Oct 2008 0:11:41 +0000 The elevation in the plasma level is at least twofold and some-times much greater. Although the reduction of a daily requirement of penicillin G from 1 million to 500,000 units has very little sig-nificance, a reduction by 50% or more may be of importance for convenience in the treatment of resistant infections that may require the administration of penicillin G in very large doses.Probenecid also retards the renal excretion of certain penicillin congeners to a variable degree that is dependent, in part, on the ratio of the amounts secreted and filtered. 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