The pharmacokinetics of single oral doses of feprazone in healthy volunteers and elderly patients.

1. The pharmacokinetics of feprazone were studied in nine healthy volunteers and 10 elderly patients. 2. The mean elimination half-life of feprazone after a single oral dose in the healthy volunteers was 22.3 h, the mean apparent clearance 0.0051 1/h per kg and the mean volume of distribution 0.1681/kg. Corresponding values for the elderly patients were 22.6 h, 0.00561/h per kg and 0.1651/kg, which are not different from those for the volunteers. Thus, we were unable to detect any changes in feprazone pharmacokinetics which are related to age, or to the concurrent use of chronic medications, such as digoxin, diuretics, or hormones.

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.

[Determination of feprazone and one of its metabolites in human plasma after high-performance liquid chromatographic or thin-layer chromatographic separation]. / Die quantitative bestimmung von feprazon und einem Feprazon-Metaboliten in Humanplasma nach hochleistungsflüssigkeitschromatographischer oder dünn-schichtchromatographischer Trennung.

Two procedures suitable for pharmacokinetic routine analysis are described for the simultaneous determination of feprazone and one of its metabolites (DA 3505) in plasma samples. After extraction from acidified plasma feprazone and DA 3505 are determined by measuring UV absorbance after thin-layer chromatographic (TLC) separation (reversed-phase TLC plates; methanol--water--formic acid) or high-performance liquid chromatographic (HPLC) separation (silica gel column; hexane--tetrahydrofuran--acetic acid). Limits of detection are 0.1 microgram feprazone per ml plasma and 0.2 microgram of its metabolite per ml plasma using the HPLC method. Concentration down to about 0.5 microgram/ml plasma of both compounds can be determined using the TLC method.

Some studies of feprazone.

Feprazone, 200 mg t.d.s., was compared with indomethacin, 25 mg t.d.s. rising to 50 mg t.d.s., in an eight-week double-blind cross-over study in twenty-three patients with active rheumatoid arthritis. Both therapies proved equally efficacious and acceptable. Measurement of the plasma levels of the two drugs showed no consistent correlation between efficacy and plasma concentrations.

Gas-chromatographic analysis of 4-prenyl-1,2-diphenyl-3-5-pyrazolidinedione (feprazone) at therapeutic levles in human plasma.

A specific and sensitive procedure for the determination of prenazone at therapeutic levels in human plasma has been developed. The method involves extraction of the drug from acidified plasma into chloroform. After further purification by back extraction the residue is examined on a gas-liquid chromatograph fitted with a flame ionisation detector. Tetraphenylethylene is used as an internal standard for quantitation by the relative peak height technique. Plasma levels encountered after oral ingestion of therapeutic doses are reported.