Brent S. Rushall, (February 2002).

PubMed Identifier 7011657
Authors - Cunningham RF. Israili ZH. Dayton PG.
Title - Clinical pharmacokinetics of probenecid. [Review] [148 refs]
Source - Clinical Pharmacokinetics. 6(2):135-51, 1981 Mar-Apr.

Abstract

A review of the clinical applications and of the disposition of probenecid in man, including drug interactions, is presented. Probenecid is the classical competitive inhibitor of organic acid transport in the kidney and other organs. There are 2 primary clinical uses for probenecid: as a uricosuric agent in the treatment of chronic gout and as an adjunct to enhance blood levels of antibiotics (such as penicillins and cephalosporins). Adsorption of probenecid is essentially complete following oral administration. The drug is extensively metabolised by glucuronide conjugation and by oxidation of the alkyl side chains; oxidation of the aromatic ring does not occur. The half-life of probenecid in plasma (4 to 12 hours) is dose-dependent. Renal excretion is the major route of elimination of the metabolites; excretion of the parent drug is minimal and is dependent on urinary pH. Probenecid and its oxidised metabolites are extensively bound to plasma proteins, mainly to albumin. Tissue concentrations (based on animal studies) are generally lower than plasma concentrations. Most of the drug-drug interactions involving probenecid are due to an effect on the kidney-block of transport of acidic drugs. Similarly probenecid affects the tubular secretion of a number of acidic endogenous substances by the kidney. Probenecid is also involved in the block of transport of acidic metabolites of catecholamines, for example homovanillic and hydroxyindoleacetic acids, in the brain. There are a number of analytical procedures for the assay of probenecid. These are based on spectrophotometry, spectrofluorometry, gas and liquid chromatography and radioimmunoassay. [References: 148]

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PubMed Identifier 1156031
Authors - Erttmann RR. Damm KH.
Title - On the problem of a common hepatic transport process for steroids. Uptake of 3-H-taurocholic acid and 3-H-corticosterone into rat liver slices.
Source - Archives Internationales de Pharmacodynamie et de Therapie. 214(2):232-9, 1975 Apr.

The uptake of 3-H-oubain (2 times 10- minus 9 and 2 times 10- minus 5 M), 3-H-taurocholic acid (2 times 10- minus 8 and 2 times 10- minus M) and 3-H-corticosterone (2 times 10- minus 9 and 2 times 10- minus 5M) into rat liver slices was investiged. The steroids were extensively accumulated as demonstrated by the following T/M ratios: ouabain: 3.82 and 3.72 resp.; taurocholic acid: 10.49 and 9.88 resp.; corticosterone: 12.84 and 8.41 resp.. Only corticosterone uptake was dependent on the medium concentration but without alterations under anaerobic conditions. The contrary could be found in case of ouabain and taurocholic acid. Further differences between the steroids investigated could be shown in experiments on the interaction with organic anions (probenecid, para-aminohippuric acid, citrate and alpha-ketoglutarate). At least no competition among the steroids concerning their uptake into liver tissue could be demonstrated. The results are discussed in contradiction to the current theories concerning the hepatic uptake of steroid compounds.

Shaw, D. (1997). Over the edge. Wantirna, Victoria, Australia: Spintex Publishing House. (pp. 125-138) Reprinted with kind permission. Available in Australia for $19.95.

Even if an athlete chooses to compete on anabolic steroids, he or she could use any one of a number of blocking agents that prevent the excretion of steroids from the kidneys, or masking drugs that confuse the test results. Probenecid was recognised as a popular blocking agent. It effectively stopped any trace of the steroids seeping into the urine. In 1984, Los Angeles, a friend of mine from the AIS successfully used Probenecid to hide the steroids he was taking. Apparently there was a rumour circulating that Probenecid might show up on the test so my friend rehearsed his excuse: he had gonorrhoea, and one of the functions of Probenecid is to increase the effectiveness of penicillin in the treatment of venereal disease. He was never called upon to make his excuse.

1. CINAHL 1092-2002 produced no references for probenecid.
2. BJSM, 31(2), 1216-8, 1997 (Hardy et al) reported on probenecid for an AFL player.
3. Probenecid is used for gout and drug resistance (particularly antibiotics).
4. Probenecid is used with drugs and chemicals that share the same parent molecule.
5. Primarily used with antibiotics and for venereal diseases (e.g., gonorhea).
6. Half-life depends upon dose (usually <12 hours normally 3-6 hours). Bigger the dose, the longer and more effectively it works but never perfectly retentive -- always some leakage.
7. Helps with anaesthesia.
8. Mostly 1970s references.
9. Works differently with corticosteroids (generally anti-inflammatories but even then differentially) but no mention of work with anabolic steroids.
10. MEDLINE search from 1983-1994 showed no articles on "anabolic steroids and probenecid."

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