Fecal blood loss during isoxicam and piroxicam administration for 28 days

After an 11-day baseline period, groups of eight healthy men received isoxicam, 200 mg once a day, or piroxicam, 20 mg once a day, for 28 days. Fecal blood loss (FBL) was quantitated by the 51Cr-labeled erythrocyte method. FBLs for both isoxicam and piroxicam were only slightly higher than baseline for the first 3 drug dosing days, confirming the results of a previously published 4-day study of piroxicam, but FBL subsequently steadily increased, with maxima occurring for most subjects receiving isoxicam in 2 or 3 weeks and for most subjects receiving piroxicam in 3 or 4 weeks. This implies that dosing for 7 days or less, as is frequent in FBL studies of nonsteroidal anti-inflammatory drugs, may be insufficient to detect the peak drug-induced FBL. In week 4, FBL for both drugs was elevated approximately 0.6 ml/day over baseline. FBLs in week 4 were comparable to those reported for naproxen and less than those reported for indomethacin and acetylsalicylic acid. Statistical analyses of weekly plasma drug minimum concentrations suggest steady state was reached at week 2 for isoxicam and week 3 for piroxicam. There were large between-subject variations in steady-state plasma drug concentrations for both drugs. One subject in each drug group indulged in excessive alcohol consumption during the medication period, with a concomitant significant increase in FBL, which suggests exacerbation of the drug effect.