A population pharmacokinetic model to predict oxypurinol exposure in patients on haemodialysis
| Autor: | Peter T. Chapman, John H Irvine, Lisa K. Stamp, Daniel F. B. Wright, Matthew P. Doogue, Nicholas B Cross, Murray L. Barclay |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male medicine.medical_specialty Gout medicine.medical_treatment Allopurinol Population Urology Renal function Oxypurinol Pharmacology 030226 pharmacology & pharmacy Models Biological Gout Suppressants 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Renal Dialysis medicine Humans Pharmacology (medical) Dosing education Dialysis Aged 030203 arthritis & rheumatology Aged 80 and over education.field_of_study business.industry General Medicine Middle Aged medicine.disease NONMEM Female business medicine.drug |
| Zdroj: | European journal of clinical pharmacology. 73(1) |
| ISSN: | 1432-1041 |
| Popis: | The aims of this study were to characterise the population pharmacokinetics of oxypurinol in patients receiving haemodialysis and to compare oxypurinol exposure in dialysis and non-dialysis patients. Oxypurinol plasma concentrations from 6 gout people receiving haemodialysis and 19 people with gout not receiving dialysis were used to develop a population pharmacokinetic model in NONMEM. Deterministic simulations were used to predict the steady-state area under the oxypurinol plasma concentration time curve over 1 week (AUC7days). The pharmacokinetics of oxypurinol were best described by a one-compartment model with a separate parameter for dialytic clearance. Allopurinol 100 mg daily produced an AUC7days of 279 μmol/L h in dialysis patients, a value 50–75 % lower than the AUC7days predicted for patients with normal renal function taking 200 to 400 mg daily (427–855 μmol/L h). Dosing pre-dialysis resulted in about a 25–35 % reduction in exposure compared to post-dialysis. Oxypurinol is efficiently removed by dialysis. The population dialytic and total (non-dialytic) clearance of oxypurinol were found to be 8.23 and 1.23 L/h, standardised to a fat-free mass of 70 kg and creatinine clearance of 6 L/h, respectively. Our results suggest that if the combination of low-dose allopurinol and haemodialysis does not result in sustained urate lowering below treatment targets (serum urate ≤0.36 mmol/L), then allopurinol doses may be increased to optimise oxypurinol exposure. |
| Databáze: | OpenAIRE |
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