Renal and gastrointestinal tolerability of lornoxicam, and effects on haemostasis and hepatic microsomal oxidation

Abstract

Three separate studies were carried out to assess the renal and gastrointestinal tolerability of lornoxicam, and its effects on haemostasis and hepatic microsomal oxidation. Haemostasis and hepatic microsomal oxidation. Six men and 6 women had salivary antipyrine half-life determined before and on the last day of 14 days' treatment with lornoxicam 4 mg twice daily. Haemostasis, coagulation and thrombolysis were assessed ex vivo using a haemostatometer before and on Day 14 of lornoxicam treatment. Lornoxicam 4 mg twice daily for 14 days had no significant influence on antipyrine elimination half-life or haemostasis, coagulation and thrombolysis. Renal tolerability. Three groups of 8 healthy young men received respectively 4, 6 and 8 mg lornoxicam twice daily by mouth for 22 days. Nephrotoxicity studies on serum and urine were done repeatedly before, during and after lornoxicam treatment. Serum and urine creatinine, serum Tamm-Horsfall glycoprotein (THG), and urine n-acetylglucosaminidase (NAG), THG and retinol binding protein (RBP) concentrations showed sporadic values outside the laboratory reference range, but these were not in any subject temporally related to drug treatment and were unrelated to dose. Urine microscopy was unremarkable. Thus this study yielded no evidence that lornoxicam has any nephrotoxic effects in healthy young men receiving doses up to 8 mg twice daily for 22 days. Gastrointestinal blood loss and endoscopy. The gastrointestinal effects of lornoxicam 4 mg, indomethacin 50 mg or placebo twice daily for 29 days were evaluated in 45 healthy men. After an initial endoscopic examination, subjects underwent 51Cr red cell labelling. Complete daily faecal collections were then made from Days 6-12, 20-26 and 34-40. Treatments were given from Days 13-41. Endoscopy was repeated 4-8 h after the last dose of medication. Faecal blood loss during lornoxicam treatment was greater than placebo and less than indomethacin, but within- and between-subject variability was such that the differences were not statistically significant. Endoscopic findings were normal in most subjects before and after all 3 treatments.