title: An investigation of acetylcholine released in skeletal muscle and protein unbound drug released in blood based on the pyridostigmine bromide (pretreatment drug) sustained-release pellets by microdialysis technique in the rabbit model.
abstract: Pyridostigmine bromide (PB) is a reversible acetylcholinesterase inhibitor that has been used as a pretreatment drug for "Soman" nerve gas poisoning in combat to increase survival. The once-daily PB-sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods in our laboratory, which was followed by zero-order release mechanism. The results showed that the released concentration of acetylcholine (ACh) in skeletal muscle and the released concentration of protein unbound drug in blood were determined by microdialysis technique to have significant differences (P<0.05) among the three dosage forms (IV injection, commercial IR tablets and the PB-SR pellet). The released concentrations of ACh and protein unbound drug for PB-SR pellets were slower than IV injection and commercial IR tablets; this phenomenon indicating that the retention period of drug efficacy in vivo for PB-SR pellet was longer than the others, that is to say, the PB-SR pellets provided with SR effect in vivo as well. We believe that once-daily administered PB-SR pellets would improve limitations of post-exposure antidotes, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in wars or terrorist attacks in the future.
authors.affiliation: Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. huangtyng.tw@yahoo.com.tw
authors.forename: Yuh-Tyng
authors.initials: YT
authors.lastname: Huang
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Cheng
authors.forename: Tsun-Fwu
authors.initials: TF
authors.lastname: Lai
authors.forename: Tong-Rong
authors.initials: TR
authors.lastname: Tsai
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
authors.forename: Wen-Ho
authors.initials: WH
authors.lastname: Chuo
authors.forename: Thau-Ming
authors.initials: TM
authors.lastname: Cham
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D002800:Cholinesterase Inhibitors / Q000097:blood* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003692:Delayed-Action Preparations; D017551:Microdialysis / Q000379:methods; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000379:methods; D011729:Pyridostigmine Bromide / Q000097:blood* / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D002800:Cholinesterase Inhibitors; D003692:Delayed-Action Preparations; D011729:Pyridostigmine Bromide; D000109:Acetylcholine