Key result
A single 250 mg oral dose of diflunisal in 6 patients with renal failure demonstrated plasma accumulation of phenolic glucuronide and sulphate conjugates.
Why the study?
How does renal failure affect the pharmacokinetics and accumulation of diflunisal and its conjugates after a single oral dose?
How does renal failure affect the pharmacokinetics and accumulation of diflunisal and its conjugates after a single oral dose?
In patients with renal failure, diflunisal clearance is decreased and its phenolic glucuronide and sulphate conjugates accumulate in plasma.
May warrant caution in renal impairment; hypothesis-generating for clinical consequences of accumulation.
Six patients with renal failure were given a single oral dose (250 mg) of diflunisal. In contrast to the acyl glucuronide, the phenolic glucuronide and sulphate conjugates showed the capacity to accumulate in plasma, suggesting that systemic instability of the acyl glucuronide contributes, via hydrolysis, to plasma concentrations of diflunisal itself. Although earlier studies in renal failure patients have almost certainly underestimated diflunisal clearance (by overestimation of plasma diflunisal concentrations through unrecognized acidic hydrolysis of diflunisal sulphate during analysis), the present results suggest that the reported decrease in clearance was not attributable only to this analytical artifact.
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Rg et al. (1991) studied renal failure (n=6). diflunisal was evaluated on plasma accumulation of conjugates and diflunisal clearance. A single 250 mg oral dose of diflunisal in 6 patients with renal failure demonstrated plasma accumulation of phenolic glucuronide and sulphate conjugates.
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