Pyridostigmine bromide and its relation to Gulf War illness

Abstract

Pyridostigmine bromide acts as a reversible cholinesterase inhibitor that is used at relatively high doses in treatment of Myasthenia gravis and in low dose regimens as prophylaxis against nerve agents poisoning during the Gulf War. The manifestation of late nonspecific symptoms commonly called Gulf War illness has led to the discussion about the role of pyridostigmine bromide in the pathogenesis of this illness. In our study, we described plasma absorption profile of pyridostigmine bromide after p.o. administration in rats; subsequently, changes in blood biochemical and oxidative stress markers were measured. Pyridostigmine bromide was applied p.o. at the dose of 5.82 mg/kg b.w. according to the previously published recommendations. The absorption of pyridostigmine was relatively fast; the C_max in plasma was 110.20 ± 15.12 ng/ml at T_max of 197.12 ± 17.14 min. The bioavailability expressed as AUC_total was 44,348 ± 7608 min ng/ml. The prolongation of pyridostigmine in circulation is in agreement with relatively long half-life that was 179.00 ± 28.54 min. Several blood biochemical markers were altered, including glucose, creatinine, creatine kinase, alanine aminotransferase, aspartate aminotransferase, interleukin-6, triglycerides, and cholesterol. However, the changes could be considered as mild. Thiobarbituric acid reactive substances and ferric reducing ability of plasma indicate suppression of basal metabolism. The results of blood biochemical and oxidative stress markers imply that long-term use might possibly change the basal metabolism and cause cellular damage with inflammatory changes.

Keywords:

• Pyridostigmine bromide
• blood biochemistry
• oxidative stress
• HPLC
• rats

Acknowledgements

The authors thank Assoc. Prof. Jaroslav Chladek for pharmacokinetic analysis. This study was supported by Ministry of Defense of the Czech Republic, the Long-Term Developing Plan 1011, Ministry of Health of the Czech Republic, the DRO of University Hospital Hradec Kralove, No. 00179906, and by the UHK Long-term development plan.

Disclosure statement

No potential conflict of interest was reported by the authors.