NEWS HIGHLIGHTS
Published Studies Related to Probenecid
Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol. [2009.01]
OBJECTIVES: To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment... CONCLUSION: This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr < or =0.30 mmol/l, following 2 months of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day.
Pharmacokinetics and tolerability of oseltamivir combined with probenecid. [2008.09]
Oseltamivir is an inhibitor of influenza virus neuraminidase, which is approved for use for the treatment and prophylaxis of influenza A and B virus infections.Alternate-day dosing of oseltamivir plus dosing with probenecid four times daily achieved trough oseltamivir carboxylate concentrations adequate for neuraminidase inhibition in vitro, and this combination should be studied further.
Reduction in non-glomerular renal clearance of the caffeine metabolite 1-methylxanthine by probenecid. [2007.08]
OBJECTIVE: Urinary caffeine metabolic ratios used to quantify the activity of numerous drug-metabolizing enzymes are an established component of cocktail approaches for metabolic phenotyping. Because in vitro evidence suggests that 1-methylxanthine (1-MX), a major caffeine metabolite, is actively secreted into urine by organic anion transporters (hOATs), coadministration of renal hOAT inhibitors like probenecid may impair these procedures... CONCLUSIONS: 1-MX undergoes renal tubular secretion which is substantially reduced by probenecid, possibly due to inhibition of renal hOATs. This inhibition may explain the influence of probenecid on urinary caffeine metabolic ratios and, thus, its impact on the assessment of enzyme activities. It also suggests that 1-MX might serve as a model substrate for the renal tubular transport of organic anions.
Effect of probenecid on the pharmacokinetics of carbamazepine in healthy subjects. [2005.06]
OBJECTIVES: Carbamazepine (CBZ) undergoes biotransformation by CYP3A4 and CYP2C8, and glucuronide conjugation. There has been no clear demonstration to reveal the role of glucuronidation in the disposition of CBZ. We evaluated the effect of probenecid, a UDP-glucuronosyltransferase inhibitor, on the pharmacokinetics of CBZ in humans... CONCLUSION: Although probenecid showed a minimal effect on the glucuronidation of CBZ and CBZ-E, it increased CBZ biotransformation to CBZ-E, most likely reflecting the induction of CYP3A4 and CYP2C8 activities, in humans. These results demonstrate that glucuronide conjugation plays a minor role in the metabolism of CBZ and CBZ-E in humans, and that probenecid has an inducing effect on the disposition of CBZ.
Different effects of three transporting inhibitors, verapamil, cimetidine, and probenecid, on fexofenadine pharmacokinetics. [2005.01]
OBJECTIVE: Fexofenadine is a substrate of P-glycoprotein and organic anion transporting polypeptides. The aim of this study was to compare the inhibitory effects of different transporting inhibitors on fexofenadine pharmacokinetics... CONCLUSION: This study suggests that verapamil increases fexofenadine exposure probably because of an increase in bioavailability through P-glycoprotein inhibition and that probenecid slightly increases the area under the plasma concentration-time curve of fexofenadine as a result of a pronounced reduction in renal clearance. However, it may be difficult to explain these interactions by simple inhibitory mechanisms on target transporters.
Clinical Trials Related to Probenecid
Safety and Tolerance of Zidovudine With Probenecid and the Effect of Probenecid on Zidovudine Pharmacokinetics Over Four Weeks [Completed]
To evaluate the interaction of probenecid with zidovudine (AZT). Because AZT is eliminated
quickly from the body, it must be taken frequently. A previous study showed that probenecid
slowed the elimination of AZT without side effects, but that study lasted only 5 days. This
study is to see whether this effect continues for 1 month and whether the continuation of
probenecid and AZT is free of side effects over 1 month.
Influence of Probenecid and Quinine on the Pharmacokinetics of Azidothymidine [Completed]
Part I studies the effect of quinine on how zidovudine (AZT) is used by the body and
eliminated through the kidneys in HIV infected patients. Part II studies the effect of
probenecid and quinine on the same aspects.
Because AZT leaves the bloodstream quickly, patients must take the drug frequently to keep
adequate amounts in their bodies. Probenecid and quinine may slow down the rate at which AZT
leaves the body. Therefore, taking these drugs along with AZT may reduce the amount of AZT
needed for treatment.
10-Propargyl-10-Deazaaminopterin Plus Probenecid in Treating Patients With Advanced Solid Tumors [Completed]
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
they stop growing or die. Probenecid may increase the effectiveness of
10-propargyl-10-deazaaminopterin by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the effectiveness of combining
10-propargyl-10-deazaaminopterin and probenecid in treating patients who have advanced solid
tumors.
Evaluation of Alternative Oseltamivir (Tamiflu) Dosing Strategies. [Completed]
Objective 1: Determine the safety and toxicity profile of Tamiflu administered in
combination with probenecid in healthy adults. Objective 2: Determine the pharmacokinetic
profile of Tamiflu and probenecid in healthy adults.
A Drug Interaction Study of VI-0521 With Metformin, Sitagliptan and Probenecid in Healthy Subjects. [Recruiting]
The purposes of this study are to:
- Find out how much of the study drugs are in the blood of healthy subjects after taking
multiple doses of VI-0521, metformin and sitagliptan.
- Determine the effect of probenecid on the amount of VI-0521 in the blood of healthy
subjects after taking multiple doses.
- Find out how much topiramate is in the semen of healthy male subjects after taking
multiple doses.
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