Parenteral ambroxol treatment causes xanthine and calcium oxalate stones in rats

Introduction: Ambroxol (ABX) is known to promote bronchial secretion and is used as an expectorant. This study was undertaken to document the connection between ambroxol parenteral treatment and bladder stones in rats. Material and Methods: Forty-five wild rats (Rattus sp.) were divided into three equal groups. Rats from the first and second groups received ABX s.c. during 2 weeks in total doses of 30 mg/kg per 24 h and 60 mg/kg per 24 h, respectively. Rats from the control group received 1 mL of injection solution s.c. One month after the treatment termination, animals were sacrificed and urinary tracts without urethra were dissected. Stones found in the bladders were measured, weighed and chemically analysed. Voiding cystography was performed to exclude pathology of the lower urinary tract. Photo documentation was produced. Results: From the first and second groups, 33% and 47% of rats, respectively, had solitary stones in the bladder. In one case from the second group, there was a huge stone in the bladder and urethra. There were no stones in rats from the control group. The mean length of stones was 1.38 +/- 0.23 mm and 1.41 +/- 0.60 mm in the first and second groups, respectively. Mean stone weight was 1.2 +/- 0.2 x 10(-3) g and 1.44 +/- 0.54 x 10(-3) g. Stones were composed of 67% of xanthine and 33% of calcium oxalate. Conclusions: Ambroxol parenteral treatment caused xanthine and oxalate stone formation. Attention should be paid to the possibility of urinary stone formation after long-term ABX treatment.