Pyridostigmine Bromide and Potassium Iodate: Subacute Oral Toxicity and Stability

Abstract

Subacute toxicity of pyridostigmine bromide (PB) and potassium iodate (PI) tablets upon forty five days administration were assessed by changes in body weight, hematology, serum biochemical parameters and histopathology of rat liver and kidney. LD 50 of PB was estimated to be 66.9 mg/kg. At dose of 45 mg/kg/day showed decrease in body weight and liver weight with cytoplasmic acidophilic bodies and vesicular steatosis signifying hepatocellular injury. Kidney tissue developed neutrophil polymorph infiltration with inflammatory glomerulonephritis, protein casts and glomerulosclerosis. Serum SGOT, SGPT, ALP and lipid profile were elevated. The oral LD 50 of PI was found to be 944.6 mg/kg. PI at 150 mg/kg dose showed anorexia and body weight loss. Serum SGOT, ALP, cholesterol and triglyceride level were elevated at 85 and 150 mg/kg dose and focal area of tubular injury and inflammatory cell infiltration occurred only at 150 mg/kg dose in kidney. The content of PB and PI has been found stable in accelerated (40 ± 2°C/75 ± 5% RH), intermediate (30 ± 2°C/65 ± 5% RH) and long term (30 ± 2°C/65 ± 5% RH) conditions. PB 30 mg/kg/day and PI 85 mg/kg/day doses are safe for rats, which are far in excess of human exposure levels.

Acute and Sub-Chronic Toxicity Assessment of Pyridostigmine Bromide 90 Mg Extended- Elease Tablets in Experimental Animals

“…We hypothesize that the feeding conditions may have contributed to the weight gain observed in both the control group and the group administered a dose of 7.2 mg/kg/day; whereas rabbits in the higher dosage group may have experienced adverse effects on their feeding capacity, resulting in insignificant weight gain. These results are consistent with the findings reported by Bigoniya et al [4].…”

“…These results are consistent with prior investigations by Morgan and Kluwe [6], [7]. Similarly, a study conducted by Bigoniya observed non-significant elevations in AST and ALT levels in rats orally administered PB at a dose of 45 mg/kg for 45 days, with no discernible effect on blood protein levels [4].…”

“…Morgan's investigation into the subchronic oral toxicity of PB in rats, utilizing doses ranging from 1 mg/ kg to 90 mg/kg over a period of 90 days [7], and Kluwe's examination of subchronic oral toxicity in dogs, employing a maximum PB dose of 20 mg/kg for 3 months [6], did not observe alterations in hematological parameters among the subjects. Similarly, in the study by Bigoniya et al involving rats treated with PB doses of 20 mg/kg, 30 mg/kg, and 45 mg/kg for 45 days, only the group administered 45 mg/kg showed a decrease in red blood cell count after 15 days of treatment; a decrease in hemoglobin after 45 days of treatment; and an increase in white blood cell count after 15 days of treatment in the groups administered PB at doses of 30 mg/kg and 45 mg/kg [4].…”