The disposition of feprazone and its hydroxylated metabolite in human volunteers.
1. 14C-Feprazone administered as a single oral dose (17 mg/subject) to each of 3 human volunteers on the 6th day of repeated dosage with unlabelled feprazone (200 mg/subject, twice daily) was excreted slowly, with only 19-38% of the dose excreted in the urine in 8 days, with a further 27-49% of the dose in the faeces. 2. 14C-Feprazone had a half-life of 30-33 h, similar to that after single dosage of unlabelled feprazone (22-33 h). The half-life for total 14C was not significantly different from that for unchanged feprazone, indicating that no metabolite with a very long half-life was formed. 3. Only feprazone and 4'-hydroxyfeprazone were detected in the plasma of subjects dosed orally with feprazone, the metabolite being characterized by mass spectrometry. The time of peak plasma concentration of feprazone was 4-5 h after dosage, and of 4'-hydroxyfeprazone was approx. 25 h. The urine contained feprazone plus its C-glucuronide, and 4'-hydroxyfeprazone plus its conjugate (glucuronide), in the ratio of approx. 5:1. 4. When 4'-hydroxyfeprazone was administered as a single oral dose to a human volunteer the plasma elimination half-life of the metabolite was 18 h, but after administration of feprazone the half-life of 4'-hydroxyfeprazone was 45 +/- 29 h (10 subjects), indicating the slow hydroxylation of feprazone and the slow excretion of 4'-hydroxyfeprazone. The clearance of feprazone was 5.2 and of 4'-hydroxyfeprazone was 5.5 ml/kg/h. 5. These studies have shown that even though enterohepatic recirculation of the drug in man is indicated, the plasma half-life of feprazone is unchanged on repeated dosage, and accumulation of the drug at a daily dosage of 2 x 200 mg, does not occur.
Berry
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Poisons Unit, New Cross Hospital, London, UK.
Parke
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D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D011298:Feprazone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005965:Glucuronates / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006900:Hydroxylation; D008297:Male; D013058:Mass Spectrometry; D010653:Phenylbutazone / Q000031:analogs & derivatives*
D002250:Carbon Radioisotopes; D005965:Glucuronates; D011298:Feprazone; D010653:Phenylbutazone