Renal effects of indoprofen in rhesus monkeys

The non-steroidal anti-inflammatory analgesic alpha-[4-(1-oxo-2-iso-indolinyl)-phenyl]propionic acid (indoprofen) was given p.o. in gelatin capsules to six groups of six Rhesus monkeys (three males and three females/group) for 15 months. Group I (five males and five females) served as control and was given empty gelatin capsules. The following daily doses were used: Group 2--20 mg/kg b.i.d.; Group 3--40 mg/kg q.d.; Group 4--30 mg/kg b.i.d.; Group 5--60 mg/kg q.d.; Group 6--40 mg/kg b.i.d. and Group 7--80 mg/kg q.d. Except for some elevated blood urea nitrogen levels after 12 months in the animals of Group 7, no changes in clinical function test values, absolute and relative kidney weights or renal gross abnormalities were found. The renal papillae and pelves were normal and not affected in all monkeys. The microscopic examination revealed a focal chronic interestitial nephritis in some of the monkeys. In the survivors the incidence of this disease increased from one out of ten control animals to three out of five monkeys in Group 7 (80 mg/kg/d). However, this quantal, statistically significant difference became biologically irrelevant and no longer statistically significant when these microscopic changes were quantified. The most severe case was seen in the control animal and the least pronounced in monkeys having received 80 mg/kg/d. When these cases of interstitial nephritis were further evaluated using a multifactorial point sampling procedure, no significant quantitative changes in renal tissue components, indicative of analgesic-induced nephropathy, were detectable.