Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol.

Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Research Abstract Details 

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Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Abstract Text:

Richard O Day,Garry G Graham,Mark Hicks,Andrew J McLachlan,Sophie L Stocker,Kenneth M Williams,

Allopurinol is the drug most widely used to lower the blood concentrations of urate and, therefore, to decrease the number of repeated attacks of gout. Allopurinol is rapidly and extensively metabolised to oxypurinol (oxipurinol), and the hypouricaemic efficacy of allopurinol is due very largely to this metabolite.The pharmacokinetic parameters of allopurinol after oral dosage include oral bioavailability of 79 +/- 20% (mean +/- SD), an elimination half-life (t((1/2))) of 1.2 +/- 0.3 hours, apparent oral clearance (CL/F) of 15.8 +/- 5.2 mL/min/kg and an apparent volume of distribution after oral administration (V(d)/F) of 1.31 +/- 0.41 L/kg. Assuming that 90 mg of oxypurinol is formed from every 100mg of allopurinol, the pharmacokinetic parameters of oxypurinol in subjects with normal renal function are a t((1/2)) of 23.3 +/- 6.0 hours, CL/F of 0.31 +/- 0.07 mL/min/kg, V(d)/F of 0.59 +/- 0.16 L/kg, and renal clearance (CL(R)) relative to creatinine clearance of 0.19 +/- 0.06. Oxypurinol is cleared almost entirely by urinary excretion and, for many years, it has been recommended that the dosage of allopurinol should be reduced in renal impairment. A reduced initial target dosage in renal impairment is still reasonable, but recent data on the toxicity of allopurinol indicate that the dosage may be increased above the present guidelines if the reduction in plasma urate concentrations is inadequate. 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. Monitoring of plasma concentrations of oxypurinol should also help to identify patients with poor adherence. Uricosuric drugs, such as probenecid, have potentially opposing effects on the hypouricaemic efficacy of allopurinol. Their uricosuric effect lowers the plasma concentrations of urate; however, they increase the CL(R) of oxypurinol, thus potentially decreasing the influence of allopurinol. The net effect is an increased degree of hypouricaemia, but the interaction is probably limited to patients with normal renal function or only moderate impairment.

Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Publishing Authors By Initials

RO Day,GG Graham,M Hicks,AJ McLachlan,SL Stocker,KM Williams,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics research

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Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Journal Published:

PUBLICATION TYPE: Review

Journal: Clinical pharmacokinetics

VOLUME: 46

Page Numbers: 623-44

Journal Abbreviation:

ISSN: 0312-5963

DAY: 30

MONTH: 11

YEAR: 2007

Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7606849

Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Keywords Mesh Terms:

KEYWORDS: Pharmacokinetics

MESH TERMS: pharmacokinetics

Chemical & Substance for Abstract: Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Information

Substance Name: Allopurinol

Registry Number: 315-30-0

Grant and Affiliation Information for Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol.

AFFILIATION: School of Medical Sciences, Faculty of Medicine, University of New South Wales and Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia. R.Day@unsw.edu.au

Country: New Zealand

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MEDLINETA: Clin Pharmacokinet

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