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  • Title: Kinetics of single doses of fenbufen in patients with renal insufficiency.
    Author: Rogers HJ, Savitsky JP, Glenn B, Spector RG.
    Journal: Clin Pharmacol Ther; 1981 Jan; 29(1):74-80. PubMed ID: 7460478.
    Abstract:
    Fenbufen (gamma-oxo[1,1'-biphenyl]-4-butanoic acid) is a nonsteroidal anti-inflammatory analgesic that is metabolized to four major metabolites: gamma-hydroxy [1,1'-biphenyl]-4-butanoic acid (II), [1,1'-biphenyl]-4-acetic acid (III), 4'hydroxy [1,1'-biphenyl]-4-acetic acid (IV), and gamma, 4'-dihydroxy [1, 1'-biphenyl]-4-butanoic acid (V). Fenbufen and metabolites II and III circulate to plasma and are pharmacologically active; metabolites IV and V are normally excreted in urine. Single 800-mg doses of fenbufen were safely administered to 10 healthy subjects and to 16 patients with varying degrees of renal insufficiency. Drug and metabolite concentrations in serum and urine were determined at intervals for 3 days. It was found that renal impairment altered the metabolic pattern of fenbufen. Although t1/2 beta was the same for fenbufen and II, their plasma levels fell. No change was found in the plasma levels of III. There was evidence of moderate cumulation in plasma of the two more polar urinary metabolites (IV, V) corresponding to the degree of renal insufficiency. The total of all five compounds excreted into the urine was diminished. To account for this, either biliary and gastrointestinal excretion increased or there may have been further hepatic biotransformation of the metabolites.
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