PHARMACOKINETICS OF SINGLE ORAL DOSES OF FEPRAZONE IN PATIENTS WITH RHEUMATOID-ARTHRITIS OR WITH IMPARIED RENAL CLEARANCE

1. The pharmacokinetics of feprazone have been studied in 10 patients with rheumatoid arthritis (RA), and in a further six patients with ren al impairment (RI) who were not suffering from rheumatoid disease. 2. For RA patients, the mean elimination half-life (t1/2) of feprazone af ter a single oral dose was 21 +/- 5 h (SD), the mean apparent clearanc e (Cl) was 0.012 +/- 0.009 l/h per kg, and the mean apparent volume of distribution (V(d)) was 0.33 +/- 0.17 l/kg. Corresponding values for RI patients were 25 +/- 13 h, 0.016 +/- 0.011 l/h per kg, and 0.46 +/- 0.24 l/kg, respectively. 3. These results show no impairment of the e limination of feprazone in RA or RI patients; V(d) and Cl are greater than in healthy young volunteers or elderly subjects, the AUC values a re lower, but t1/2 values are similar in all groups. 4. It is suggeste d that the greater Cl and V(d), and lower AUC, in RA and RI patients m ay be due to renal insufficiency and decreased plasma protein binding of feprazone and its metabolite, or to induction of glucuronyl transfe rase activity by the prior medication, thus enhancing the formation of the major metabolite, the C(4)-glucuronide, and increasing drug elimi nation.