Treatment of gonorrhoea with procaine penicillin plus probenecid.

Lesinski, J; Dzierżanowska, D; Szymczak, Marek; Linda, H; Wiśniewska, C; Nawara, Abdallah; Winogrodzka, Ania

doi:10.1136/sti.49.4.358

Cited by 3 publications

(3 citation statements)

References 7 publications

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“…Some DDIs, such as penicillin and probenecid, are well established and have been put to clinical use; the half-life of penicillin is greatly prolonged by coadministration of probenecid, an OAT inhibitor (45)(46)(47). In contrast, some DDIs can lead to dire consequences.…”

Section: Ddis and Drug-metabolite Interactionsmentioning

confidence: 99%

“…Historically, probenecid was used to limit renal penicillin elimination where there was a critically small supply (45). It was later used to augment the effect of penicillin in the treatment of gonorrhea and other systemic infections (46). Probenecid is also used to block uric acid reabsorption in the proximal tubule for the treatment of gout (47); as discussed below, uric acid is a substrate of several proximal tubule drug transporters, including BCRP (ABCG2), OAT1, OAT3, and the related OAT family member (URAT1).…”

Section: Drugs and Toxinsmentioning

confidence: 99%

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Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters

Nigám¹,

Wu²,

Bush³

et al. 2015

Clinical Journal of the American Society of Nephrology

228

192

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The proximal tubule of the kidney plays a crucial role in the renal handling of drugs (e.g., diuretics), uremic toxins (e.g., indoxyl sulfate), environmental toxins (e.g., mercury, aristolochic acid), metabolites (e.g., uric acid), dietary compounds, and signaling molecules. This process is dependent on many multispecific transporters of the solute carrier (SLC) superfamily, including organic anion transporter (OAT) and organic cation transporter (OCT) subfamilies, and the ATP-binding cassette (ABC) superfamily. We review the basic physiology of these SLC and ABC transporters, many of which are often called drug transporters. With an emphasis on OAT1 (SLC22A6), the closely related OAT3 (SLC22A8), and OCT2 (SLC22A2), we explore the implications of recent in vitro, in vivo, and clinical data pertinent to the kidney. The analysis of murine knockouts has revealed a key role for these transporters in the renal handling not only of drugs and toxins but also of gut microbiome products, as well as liverderived phase 1 and phase 2 metabolites, including putative uremic toxins (among other molecules of metabolic and clinical importance). Functional activity of these transporters (and polymorphisms affecting it) plays a key role in drug handling and nephrotoxicity. These transporters may also play a role in remote sensing and signaling, as part of a versatile small molecule communication network operative throughout the body in normal and diseased states, such as AKI and CKD.

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Section: Ddis and Drug-metabolite Interactionsmentioning

confidence: 99%

Section: Drugs and Toxinsmentioning

confidence: 99%

Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters

Nigám¹,

Wu²,

Bush³

et al. 2015

Clinical Journal of the American Society of Nephrology

228

192

View full text Add to dashboard Cite

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“…In the 1940s, i05 U of benzylpenicillin was sufficient to cure anterior urethritis, whereas 20 years later, 2.4 x 106 U often was not curative (6,16). Failure rates were greatly reduced, however, in trials in which probenecid was administered orally before the intramuscular injection of benzylpenicillin (16,17,21,24). Probenecid [p-(dipropylsulfamyl)benzoic acid] blocks the renal tubular secretion of benzylpenicillin into urine, thereby producing an increase in the benzylpenicillin concentration in plasma of two-to fourfold (3).…”

mentioning

confidence: 99%

Probenecid: antibacterial action against Neisseria gonorrhoeae and interaction with benzylpenicillin

Catlin¹

1984

Antimicrob Agents Chemother

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Neisseria gonorrhoeae strains were used in an investigation of the antibacterial action of probenecid and its interaction with benzylpenicillin. The growth of 112 routine isolates was inhibited by probenecid at concentrations of 100 to 500 micrograms/ml incorporated in agar. Additive or synergistic effects of benzylpenicillin-probenecid combinations were graphically illustrated in gradient plates. In agar dilution tests with a resistant gonococcal strain, the MICs of benzylpenicillin alone and probenecid alone were 0.8 and 500 micrograms/ml, respectively; in contrast, the MICs of combinations of benzylpenicillin and probenecid were 0.45 and 75 micrograms/ml and 0.3 and 150 micrograms/ml, respectively. High concentrations of probenecid in broth were bactericidal. Probenecid alone at 50 to 100 micrograms/ml had little antibacterial effect, but in combination with an appropriate concentration of benzylpenicillin, it produced reductions of CFU in 6 h that were 100 to 300 times that produced by benzylpenicillin alone. Thus, in addition to its well-known pharmacological effects, probenecid potentiates the in vitro action of benzylpenicillin for gonococci. I suggest that synergism contributes to the beneficial effect of the benzylpenicillin-probenecid regimen for the treatment of gonorrhea. Furthermore, synergism may explain the reduction in the ratio of partially benzylpenicillin-resistant N. gonorrhoeae strains to benzylpenicillin-susceptible strains that occurred in the United States between 1972 and 1978.

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A controlled study of mezlocillin in uncomplicated acute gonorrhoea

Khan

Tomkyns

1982

Current Medical Research and Opinion

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In a randomized trial, 149 patients with uncomplicated gonorrhoea were treated with a single intramuscular dose of 1.0 g mezlocillin, 150 with 2.0 g ampicillin plus 1.0 g probenecid orally and 150 with a single dose of 1.8 mega units of procaine penicillin. Cure rates at 3, 10 and 17 days after treatment were 97%, 99% and 96% for mezlocillin, 95%, 99% and 95% for ampicillin, and 97%, 98% and 98% for procaine penicillin, respectively. The incidence of post-gonococcal urethritis was 11.3% for ampicillin plus probenecid, 10.9% for procaine penicillin and 10.5% for mezlocillin. Side-effects after all three regimens were minimal.

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Treatment of gonorrhoea with procaine penicillin plus probenecid.

Cited by 3 publications

References 7 publications

Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters

Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters

Probenecid: antibacterial action against Neisseria gonorrhoeae and interaction with benzylpenicillin

A controlled study of mezlocillin in uncomplicated acute gonorrhoea

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