• Title/Summary/Keyword: Probenecid

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Inhibitory Effect of Probenecid on Osteoclast Formation via JNK, ROS and COX-2

  • Cheng, Mi Hyun;Kim, Sung-Jin
    • Biomolecules & Therapeutics
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    • v.28 no.1
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    • pp.104-109
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    • 2020
  • Probenecid is a representative drug used in the treatment of gout. A recent study showed that probenecid effectively inhibits oxidative stress in neural cells. In the present study, we investigated whether probenecid can affect osteoclast formation through the inhibition of reactive oxygen species (ROS) formation in RAW264.7 cells. Lipopolysaccharide (LPS)-induced ROS levels were dose-dependently reduced by probenecid. Fluorescence microscopy analysis clearly showed that probenecid inhibits the generation of ROS. Western blot analysis indicated that probenecid affects two downstream signaling molecules of ROS, cyclooxygenase 2 (COX-2) and c-Jun N-terminal kinase (JNK). These results indicate that probenecid inhibits ROS generation and exerts antiosteoclastogenic activity by inhibiting the COX-2 and JNK pathways. These results suggest that probenecid could potentially be used as a therapeutic agent to prevent bone resorption.

Drug Interaction of Nalidixic Acid and Probenecid in Rabbits (Nalidixic Acid와 Probenecid의 약물 상호 작용)

  • 최준식
    • YAKHAK HOEJI
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    • v.27 no.2
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    • pp.133-138
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    • 1983
  • The interaction between nalidixic acid and probenecid was studied pharmacokinetically in rabbits. The blood level and the area under the concentration curve(AUC) of nalidixic acid administered orally in dose of 100mg/kg was elevated by the coadministration of probenecid. Probenecid inhibited both the urinary excretion and the biliary excretion of nalidixic acid. Therefore, biological half-life of nalidixic acid was prolonged by the coadministrarion of probenecid. It was considered that the coadmini-stration of probenecid is more desirable than the single administration of nalidixic acid for the therapeutic effect.

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Effect of Probenecid on Tetraethylammonium (TEA) Transport Across Basolateral Membrane of Rabbit Proximal Tubule

  • Choi, Tae-Ryong;Kim, Yong-Keun
    • The Korean Journal of Physiology
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    • v.30 no.2
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    • pp.249-256
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    • 1996
  • The effect of probenecid on the transport of tetraethylammonium (TEA) was studied in renal cortical slices and isolated membrane vesicles to investigate the interaction of organic anion with the organic cation transport system in proximal tubule. Probenecid reversibly inhibited TEA uptake by renal cortical slices in a dose-dependent manner over the concentration range of 1 and 5 mM. The efflux of TEA was not affected by the presence of 3 mM probenecid. Kinetic analysis indicated that probenecid decreased Vmax without significant change in Km. Probenecid inhibited significantly tissue oxygen consumption at concentrations of 3 and 5 mM. However, probenecid did not significantly reduce TEA uptake in brush border and basolateral membrane vesicles prepared from renal cortex even at a concentration as high as 10 mM. These results indicate that probenecid reduces TEA uptake in cortical slices by inhibiting tissue metabolism rather than by an interaction with the organic ration transporter.

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Drug Interaction of Probenecid and Lithium Carbonate (프로베네시드와 탄산리튬의 약물상호작용)

  • Lee, Jin-Hwan;Lee, Chong-Ki
    • Journal of Pharmaceutical Investigation
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    • v.17 no.2
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    • pp.95-98
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    • 1987
  • The drug interaction between probenecid and lithium carbonate was studied pharmacokinetically in rabbits. The blood level and the area under the concentration curve (AUC) of lithium carbonate administered orally were elevated by coadministration of probenecid. Probenecid inhibited the urinary excretion of lithium carbonate in rabbits. Biological half-life and $t_{max}$ of lithium carbonate were prolonged by coadministration of probenecid. From these results, dosage regimen of lithium carbonate is considered to be adjusted for effective and safe therapy in the coadministration of probenecid.

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Pharmacokinetic Interaction of Vancomycin and Probenecid in Rabbits (반코마이신과 프로베네시드의 약물동태학적 상호작용)

  • Lee, Do-Nil;You, Jae-Sin;Burm, Jin-Pil;Choi, Jun-Shik
    • Journal of Pharmaceutical Investigation
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    • v.27 no.1
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    • pp.51-56
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    • 1997
  • This study was attempted to investigate the pharmacokinetic interaction of vancomycin (10 mg/kg, i.v.) and probenecid (7.5. 15, and 30 mg/kg, oral) in rabbits. The area under curve (AUC) of plasma vancomycin concentration was significantly increased (p<0.01) in rabbits when the probenecid was coadministrated. Volume of distribution (Vd) was significantly decreased (p<0.05) in rabbits coadministrated with probenecid (15 and 30 mg/kg) and total body clearance (CLt) was decreased significantly (p<0.05. p<0.01) in rabbits coadministrated with probenecid (7.5, 15 and 30 mg/kg). There was significant correlation between AUC and probenecid dose. From the results of this experiment, it is desirable to adjust dosage regimen of vancomycin for reduction of side or toxic effect when the probenecid is coadministered in clinical practice.

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Probenecid inhibit $\alpha$-adrenergic receptor mediated vasoconstriction (프로베네시드의 혈관 알파 수용체 길항 작용)

  • Kim, Sung-Jin
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2001.11a
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    • pp.98-98
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    • 2001
  • It has been suggested that hyperuricemia is related to the development of essential hypertension. Hypertensive patients with hyperuricemia has decreased glomerular filtration activity as compared to normotensive patients with hyperuricemia. These studies indicates uric acid concentrations in blood is associated with hypertension, Probenecid is an uricosuric agent which decreases uric acid reabsorption at the proximal tubule. Recently, we have shown that probenecid exerts anti-hypertensive action in Spontaneously Hypertensive Rats. Considering these results, I have designed a series of experiments to explore potential mechanism of antihypertensive action, of probenecid. In isolated rat thoracic aorta. probenecid significantly prevented phenylephrine-induced contraction of the blood vessel. When endothelium removed blood vessels were used, probenecid produced same effect as the intact blood vessels, indicating that probenecid directly act through the ${\alpha}$ -adrenergic receptor in vascular smooth muscles rather than through endothelium. These results suggest that one of the mechanism of antihypertensive effects of probenecid is due to the direct inhibition of ${\alpha}$ -adrenergic receptor in blood vessels.

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Effect of Probenecid on the Pharmacokinetic Behavior of Pranoprofen in Rats (흰쥐에서 프로베네시드가 프라노푸로펜의 약동학적 거동에 미치는 영향)

  • Li, Xiu-Guo;Piao, Yong-Ji;Choi, Jun-Shik
    • Journal of Pharmaceutical Investigation
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    • v.35 no.6
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    • pp.397-402
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    • 2005
  • The purpose of this study was to investigate the effect of probencid on the pharmacokinetics of oral pranoprofen in rats. Pranoprofen (5 mg/kg) was coadministered with 5, 10 or 20 mg/kg of probenecid orally. Coadministration of probenecid significantly altered the pharmacokinetics of pranoprofen at 10 and 20 mg/kg. Compared with the control group, probenecid significantly (p<0.05) increased the absorption rate constant $(K_{a})$, the peak concentrations $(C_{max})$ and accordingly the area under the plasma concentration-time curve (AUC) of pranoprofen at the dose level of 10 mg/kg and 20 mg/kg of probenecid. The relative bioavailability (RB%) of pranoprofen was 1.64- to 1.82- fold increased. Furthermore, 10 and 20 mg/kg probenecid induced the decreased elimination constants $(K_{el})$ and the prolonged half-lives $(t_{1/2})$ of pranoprofen with significance (p<0.05). Coadministration of 10 and 20 mg/kg of probenecid lowered the excreted amounts of pranoprofen in the urine by 21.3-22.5% compared to the control. Overall, probenecid enhanced the bioavailability of pranoprofen and decreased its elimination rate to a greater degree at higher dose. Based on the effect of probenecid on the pharmacokinetic behavior of pranoprofen, the dosage regimen of pranoprofen should be taken into consideration when pranoprofen is administered with probenecid in the clinical setting to the patients especially with peptic ulcer or renal failure.

Drug-Biomacromolecule Interaction (VI) Binding of Nalidixic Acid and Probenecid to Bovine Serum Albumin (약물과 생체고분자간의 상호작용(VI) Nalidixic Acid 및 Probenecid와 우혈청 단백간의 결합에 관한 연구)

  • 김종국;임연수;양지선
    • YAKHAK HOEJI
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    • v.27 no.4
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    • pp.257-261
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    • 1983
  • Binding of nalidixic acid which is used primarily in the treatment of urinary infection and probenecid which is used as a uricosuric agent to bovine serum albumin were studied using difference spectrophotomeric method. 2-(4'-Hydroxybenzeneazo) bcnzoic acid as a spectrophotometric probe was used for measuring the binding of nalidixic acid and probenecid to bovine serum albumin. The association constants of nalidixic acid and probenecid were $1.58{\times}10^{4}M^{-1}$ and $1.70{\times}10^{4}M^{-1}$, respectively.

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Effect of Probenecid on Urate Excretion in the Cat Kidney

  • Jung, Dong-Keun;Kim, Yong-Keun;Jung, Jin-Sup;Lee, Sang-Ho
    • The Korean Journal of Physiology
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    • v.25 no.1
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    • pp.37-48
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    • 1991
  • The characteristics of probenecid effect on renal urate excretion in the cat were studied by clearance method and compared with those in the rabbit. In the cat GFR was $3.03{\pm}0.09\;ml/min{\cdot}kg$, and endogenous plasma urate concentration was $1.12{\pm}0.57\;{\mu}g/ml$, which is less than that in the rabbit $(3.33{\pm}0.46\;{\mu}g/ml)$. In the rabbit, $FE_{ur}$ was $1.76{\pm}0.08$ and net urate secretion was observed, while, in the cat $FE_{ur}$ was $0.70{\pm}0.02$ and net reabsorption was observed. In the cat $FE_{ur}$ was dependent on urine flow and independent of plasma urate concentration. In the rabbit $FE_{ur}$ was suppressed by infusion of probenecid $(30\;mg/kg\;-0.6\;mg/kg{\cdot}min)$ into femoral vein. In the cat the same dose of probenecid increased $FE_{ur}$ and concomitantly increased urine flow. Thus, an increase in $FE_{ur}$ by probenecid could be considered to be resulted from a change in urine flow. In the cat infusion of probenecid $(2.5\;mg/kg{\cdot}min)$ into renal artery markedly suppressed $FE_{P\;A\;H}$, but the effects on $FE_{ur}$ and urine flow were similar to those when probenecid was infused into femoral vein. These results indicate that in the cat kidney urate filtered through glomerulus is reabsorbed by a probenecid-insensitive mechanism with no evidence for net secretion.

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Drug Interaction of Probenecid and Nolidixic Acid( II ) (Probenecid와 Nalidixic Acid의 약물상호작용(藥物相互作用) ( II ))

  • Choi, Jun-Shik;Lee, Jin-Hwan;Kim, Yong-Hyun;Lee, Min-Hwa
    • Journal of Pharmaceutical Investigation
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    • v.13 no.4
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    • pp.183-190
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    • 1983
  • The interaction between probencid and nalidixic acid was studied pharmacokinetically in rabbits infused with or without acidic soiution (5% $NH_4Cl$). The results were as fellows. The blood level and the area under the blood concentration curve of nalidixic acid administered intravenously was elevated by coadministration of probenecid and more elevated in rabbits infused with acidic solution. Probenecid inhibited the urinary excretion of nalidixic acid in rabbits infused with adidic solution. Therefore, biolgcal half-life of nalidixic acid was prolonged by coadministration of probencid.

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