Pharmacokinetic and Pharmacodynamic Interaction Between Allopurinol and Probenecid in Patients with Gout

  title={Pharmacokinetic and Pharmacodynamic Interaction Between Allopurinol and Probenecid in Patients with Gout},
  author={Sophie Lena Stocker and Garry G Graham and Andrew J. McLachlan and Kenneth Mapson Williams and Richard Osborne Day},
  journal={The Journal of Rheumatology},
  pages={904 - 910}
Objective. To investigate the pharmacokinetic and pharmacodynamic interaction between probenecid and oxypurinol (the active metabolite of allopurinol) in patients with gout. Methods. This was an open-label observational clinical study. Blood and urine samples were collected to measure oxypurinol and urate concentrations. We examined the effects of adding probenecid to allopurinol therapy upon plasma concentrations and renal clearances of urate and oxypurinol. Results. Twenty patients taking… 

Figures and Tables from this paper

The pharmacokinetics of oxypurinol in people with gout.

This first established pharmacokinetic model provides a tool to achieve target oxypurinol plasma concentrations, thereby optimizing the effectiveness and safety of allopur inol therapy in gouty patients with various degrees of renal impairment.

The population pharmacokinetics of allopurinol and oxypurinol in patients with gout

The pharmacokinetic model provides a means of predicting the allopur inol dose required to achieve target oxypurinol plasma concentrations for patients with different magnitudes of renal function, different body mass and with or without concomitant diuretic use.

Understanding the dose-response relationship of allopurinol: predicting the optimal dosage.

A high baseline plasma urate concentration requires a high dose of allopurinol to reduce Plasma urate below recommended concentrations, and this dose is dependent on only the pre-treatment plasma Urate concentration and is not influenced by CLcr.

Allopurinol: insights from studies of dose–response relationships

This review covers the metabolism and pharmacokinetics of allopurinol and its active metabolite, oxypur inol and how these factors affect the plasma concentrations of urate at initiation and during long-term therapy with allopURinol.

Efficacy and Tolerability of Probenecid as Urate-lowering Therapy in Gout; Clinical Experience in High-prevalence Population

Probenecid has moderate efficacy as ULT in clinical management of patients with complex gout who have a lack of efficacy or intolerance to allopurinol and patients with chronic kidney disease may respond to probenecid with similar rates of adverse events.

Clinical Pharmacokinetics and Pharmacodynamics of Febuxostat

The pharmacokinetic parameters of febuxostat after multiple oral dose administration are not affected by mild to moderate hepatic impairment, and there is no consensus on whether renal impairment has any effect on the pharmacokinetics of feBUXostat.

Predicting Response or Non-response to Urate-Lowering Therapy in Patients with Gout

Careful examination of medication adherence, titration of doses, and the addition of uricosuric agents increase the percentage of patients responding to allopurinol and febuxostat and the proportion of patients achieving adequate lowering of serum urate.

Predicting allopurinol response in patients with gout.

Contrary to current guidelines, the model predicted that allopurinol dose requirements were determined primarily by differences in body size and diuretic use, which was found to be significant covariates.

Urate-lowering therapy for the management of gout: a summary of 2 Cochrane reviews.

There is currently moderate quality data supporting the efficacy and safety of allopurinol, febuxostat, benzbromarone, and probenecid in gout and there is insufficient evidence currently with respect to the cost-effectiveness or the most optimal sequencing of urate-lowering therapy.

Pharmacokinetics considerations for gout treatments

Canakinumab appears to be a good alternative for patients with contraindications to colchicine, NSAIDs and corticosteroids, and co-prescription with strong CYP3A4 or P-glycoprotein inhibitors can greatly modify its pharmacokinetics is to be avoided.



Clinical Pharmacokinetics and Pharmacodynamics of Allopurinol and Oxypurinol

Measurement of plasma concentrations of oxypurinol in selected patients, particularly those with renal impairment, may help to decrease the risk of toxicity and improve the hypouricaemic response.

Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients

Allopurinol 200–300 mg/day was shown to be a less potent alternative for most selected patients to attain target sUr levels (13% success), and the addition of probenecid proves to be an effective treatment strategy for attaining sUr target levels.

The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout

Allomaron® was superior to allopurinol alone in lowering serum uric acid, probably because of the added uricosuric effect of benzbromarone.

Kinetics of allopurinol and oxipurinol after chronic oral administration. Interaction with benzbromarone

The pharmacokinetic parameters of allopurinol were not modified by the uricosuric therapy, but those of oxipur inol were markedly altered by concurrent administration even of the lower dose of benzbromarone.

A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300–600 mg/day versus benzbromarone 100–200 mg/day in patients with gout

Increasing the allopurinol dose from 300 to 600 mg/day and the benzbromarone dose from 100 to 200 mg/ day according to the target sUr produced significantly higher success rates (both 78% successful in attaining sUr ⩽0.30 mmol/l).

Febuxostat compared with allopurinol in patients with hyperuricemia and gout.

Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups andFebuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily doses of 300 mg in lowering serum urate.

Uric acid lowering effect of oxipurinol sodium in hyperuricemic patients - therapeutic equivalence to allopurinol.

Oxipurinol sodium is well absorbed and sufficiently effective in hyperuricemic patients when administered as a rapid release preparation of oxipur inol sodium in a multicenter, randomized, double blind crossover trial in 99 hyperurICemic patients with normal renal function.

Observations on the disposition of probenecid in patients receiving allopurinol.

The present studies illustrate an additional complex feature of interactions between allopurinol and probenecid in man as a substrate and an inhibitor of xanthine oxidase and thus it can inhibit its own metabolism.

Kinetics of allopurinol and its metabolite oxypurinol after oral administration of allopurinol alone or associated with benzbromarone in man. Simultaneous assay of hypoxanthine and xanthine by gas chromatography‐mass spectrometry

The action of the two agents may be synergistic and not antagonistic, a pharmacological justification for the therapeutic use of this drug association and its role on the blood uric acid lowering action is complex.

Does benzbromarone in therapeutic doses raise renal excretion of oxipurinol?

The hypouricaemic effect of the combined therapy turned out to be stronger than that observed after monotherapy with allopurinol, due to the uricosuric component of benzbromarone.