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Population Pharmacokinetic Models of Oxypurinol in Adults: A Systematic Review
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DOI：10.2174/0113892002439476260101094935.png)
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Abstract
En 中文
Introduction Allopurinol and its active metabolite, oxypurinol, reduce uric acid concentrations through xanthine oxidase inhibition by suppressing the conversion of hypoxanthine and xanthine. Oxypurinol plays a prominent role in allopurinol's pharmacological activity due to its longer elimination half-life. Despite decades of clinical use, establishing an optimal dosing strategy to consistently achieve the target serum uric acid concentration lower than 0.36 mmol L-1 remains challenging. This review aimed to summarize the development of population pharmacokinetic modeling for oxypurinol and analyze factors influencing its pharmacokinetic variability.Methods PubMed, Web of Science, and Scopus were systematically searched from database inception until January 2025, adhering to the PRISMA guideline. Studies were eligible if they involved oxypurinol population pharmacokinetic analyses in adults receiving allopurinol and employed nonlinear mixed-effects modeling.Results Eight studies met the inclusion criteria, mostly involving adult gout patients. Pharmacokinetic analyses of oxypurinol employed a one-compartment model, incorporating first-order absorption and elimination, reporting clearance value of 0.60-1.74 L h-1 and volume of distribution 38.1-59.3 L. Covariates associated with oxypurinol clearance included creatinine clearance, body weight, normal fat mass, fat-free mass, ethnicity, genetic polymorphisms, and concomitant diuretics; whereas, total body weight was found as significant predictors for volume of distribution.Discussions Reported values for oxypurinol clearance and volume of distribution varied across studies. The small sample sizes and underrepresentation of certain populations, particularly Asians, restrict the generalizability of these findings.Conclusion Further research involving larger, more diverse cohorts is needed to refine therapeutic drug monitoring and identify potential covariates across different populations to optimize allopurinol therapy.
Keywords:
Allopurinol
oxypurinol
population pharmacokinetics
uric acid level
nonlinear mixed-effects model
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