Influence of probenecid on serum penicillin concentration after oral administration of penicillin

Frisk, A. Rune; Diding, N; Wallmark, G

doi:10.3109/00365515209060641

Cited by 10 publications

(4 citation statements)

References 6 publications

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“…Intracellular GSH levels were partially preserved in both XY-and XX-neurons when treated with probenecid or NAC alone, and this effect was additive when the two drugs were used in combination ( p = 0.007 probenecid alone vs. Pro-NAC; p = 0.023 NAC alone vs. Pro-NAC). A difference between XY-and XX-neurons in GSH was not observed (F [1,28] = 0.150, p = 0.701).…”

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confidence: 84%

“…1A) (n = 4 independent wells/sex/group; both p < 0.001). Group differences were observed (F [4,28] = 46.98, p < 0.0001). Intracellular GSH levels were partially preserved in both XY-and XX-neurons when treated with probenecid or NAC alone, and this effect was additive when the two drugs were used in combination ( p = 0.007 probenecid alone vs. Pro-NAC; p = 0.023 NAC alone vs. Pro-NAC).…”

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confidence: 90%

“…Probenecid is currently in clinical use to treat uric acidemia and as an antibiotic adjunct, and was developed during World War II (Benemid) to increase the bioavailability of penicillin, in short supply at the time, to wounded soldiers. 27,28 NAC is the antidote for acetaminophen/paracetamol overdoses, reducing the risk of hepatic necrosis and fulminant liver failure. 29 A randomized clinical trial of systemically administered NAC after TBI has shown positive results.…”

Section: Probenecid and Nac After Stretch-injury In Neuronsmentioning

confidence: 99%

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Probenecid and N-Acetylcysteine Prevent Loss of Intracellular Glutathione and Inhibit Neuronal Death after Mechanical Stretch Injury In Vitro

Empey

et al. 2016

Journal of Neurotrauma

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Probenecid and N-acetylcysteine (NAC) can preserve intracellular levels of the vital antioxidant glutathione (GSH) via two distinct biochemical pathways. Probenecid inhibits transporter-mediated GSH efflux and NAC serves as a cysteine donor for GSH synthesis. We hypothesized that probenecid and NAC alone would maintain intracellular GSH concentrations and inhibit neuronal death after traumatic stretch injury, and that the drugs in combination would produce additive effects. Sex-segregated rat primary cortical neurons were treated with probenecid (100 μM) and NAC (50 μM), alone and in combination (Pro-NAC), then subjected to mechanical stretch (10s strain rate, 50% membrane deformation). At 24 h, both probenecid and NAC inhibited trauma-induced intracellular GSH depletion, lactate dehydrogenase (LDH) release, and propidium iodide (PI) uptake in both XY- and XX-neurons. Combined Pro-NAC treatment was superior to probenecid or NAC alone in maintenance of intracellular GSH and neuronal death assessed by PI uptake. Interestingly, caspase 3 activity 24 h after mechanical trauma was more prominent in XX-neurons, and treatment effects (probenecid, NAC, and Pro-NAC) were observed in XX- but not XY-neurons; however, XY-neurons were ultimately more vulnerable to mechanical stretch-induced injury than their XX counterparts, as was evidenced by more neuronal death detected by LDH release and PI uptake. In addition, after stretch injury in HT22 hippocampal cells, both NAC and probenecid were highly effective at reducing oxidative stress detected by dichlorofluorescein fluorescence. These in vitro data support further testing of this drug combination in models of traumatic neuronal injury in vivo.

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confidence: 84%

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confidence: 90%

Section: Probenecid and Nac After Stretch-injury In Neuronsmentioning

confidence: 99%

See 1 more Smart Citation

Probenecid and N-Acetylcysteine Prevent Loss of Intracellular Glutathione and Inhibit Neuronal Death after Mechanical Stretch Injury In Vitro

Empey

et al. 2016

Journal of Neurotrauma

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“…procaine penicillin seemed to be near the maximum single-session dose. Meads, Knight, and Izlar (1951) and Frisk, Diding, and Wallmark (1952) have reported that the enhancement of serum penicillin levels by probenecid is dose-related up to 4 g., and Boger and Strickland (1955) suggested that toxicity as a result of shortterm administration of this drug was minimal. Recently, Cornelius, Schroeter, Lester, and Martin (1971) and the British Medical J7ournal (1968) (quoting unpublished observations of F. R. Curtis) reported that the use of 2 g. probenecid in combination with large doses of procaine penicillin caused no serious side-effects.…”

Section: Clinical Observationsmentioning

confidence: 99%