and peak plasma levels occur at 2 to 3 hours after oral dosing. The drug is eliminated almost exclusively via the kidneys in the urine (Williams, 1984).

Side effects of PB are generally related to the large doses given to myasthenics; in surgical patients, adverse reactions are controlled by simultaneous administration of atropine (Williams, 1984). Adverse reactions may be muscarinic or nicotinic (also see Chapter 5), both reactions are due to increased acetylcholine (ACh). Muscarinic reactions include nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis, and heavy perspiration. Nicotinic effects are chiefly muscle cramps, fasciculations, and weakness (Williams, 1984).

During the Gulf War, PB was used as a pretreatment for possible exposure to nerve agents because of its ability to reversibly bind to acetylcholinesterase (AChE).2 The bound fraction is thereby protected from subsequent exposure to nerve agents that would irreversibly bind to AChE. PB is not an antidote (i.e., it has no value when administered after nerve agent exposure) and is not a substitute for atropine or 2-pralidoxime chloride; rather, it enhances their efficacy (Madsen, 1998).

PB was used as an investigational product during the Gulf War (Rettig, 1999) and was not recommended for routine use. The FDA, under a then newly enacted interim rule, had granted DoD a waiver from the requirement to obtain informed consent from service members taking this drug, but the rule did not address the record keeping that would ordinarily accompany the use of an investigational drug (FDA, 1990; Rettig, 1999). PB was manufactured for Duphar and Roche; it was produced by two different facilities outside the United States, specifically in the Netherlands for Duphar and in the United Kingdom for Roche.

The Department of Defense (DoD) reported that 5,328,710 doses were fielded and estimated that approximately 250,000 personnel took at least some PB during the Gulf War.3 It was supplied as a 21-tablet blister pack, the dosage prescribed was one 30-mg tablet every 8 hours.4 Variation in use occurred, how-

2  

AChE is an enzyme necessary to remove ACh. Acetylcholine transmits nerve signals at the cholinergic neuromuscular junction or synapses in the central nervous system. Anticholinesterase agents inhibit (inactivate) AChE, resulting in an accumulation of ACh. The accumulation repetitively activates the ACh receptors, resulting in exaggerated responses of the organ (e.g., excess salivation).

3  

The number of doses fielded was obtained through a search of the Defense Personnel Support Center archived logistic records for Operations Desert Shield and Desert Storm and reflects the amount of product ordered and sent through supply channels. In most cases, only a review of each individual’s medical treatment record would provide the actual number of doses administered, and few records were maintained by individuals (Office of the Secretary of Defense Bernard Roskter, January 30, 1998 letter to the Honorable Arlen Specter, Chairman, Committee on Veterans’ Affairs, U.S. Senate, 1998).

4  

PB was distributed as 30-mg tablets in a blister pack of 21 tablets within a sealed pouch. Each packet provided a 1-week supply of PB for one person. Military personnel were issued two blister packs each. Recommended long-term storage was at 2–80°C, and blister packs removed from refrigeration were to be used within 6 months (Madsen, 1998).



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