|
|
Completed Research Projects
Title: Male/Female Differential Tolerances to Pyridostigmine Bromide
Synopsis: This study compared the effects of pyridostigmine bromide (PB) on men and women.
Overall Summary: See project objective.
Overall Project Objective: Determine if males and females have different tolerances to doctrinal dose (30 mg every 8 hours) of pyridostigmine bromide.
Results to Date: Results from this study indicate that pyridostigmine is safe. Expected side effects, primarily gastrointestinal, were observed. Other events did not appear to be related to the drug since the reporting incident was equal in active drug and placebo groups. No differences in side effects were found related to gender or weight although, as noted below, pharmacokinetic effects are both gender and weight dependent. The pharmacokinetic model that best fit pyridostigmine plasma levels was a two-compartment open model with first-order absorption, a lag time, and first-order elimination from the central compartment. The pharmacokinetic model that best fit red blood cell acetycholinesterase activity was an inhibitory Emax model with an effect compartment linked to the central compartment. The results showed that the pharmacokinetics of pyridostigmine bromide are both gender and weight dependent. The pharmacodynamic effect does not lag significantly from the plasma concentration and returns to near normal within 8 hours. With the present dosage of regimen of 30 mg every 8 hours, 30% of individuals may not have red blood cell acetylcholinesterase inhibition > 10% at the time of the trough.
Project: DOD-11
Agency: Department Of Defense
Location: South Florida Drug Research Miami FL
P.I. Name: K Lasseter
Status: Complete
Study Start Date: October 01, 1994
Estimated Completion Date: February 01, 1998
Specific Aims: To evaluate the tolerance of pyridostigmine bromide (30 mg every 8 hours for 21 days); to evaluate multiple dose kinetics; and to evaluate the effect of weight in males and females upon drug tolerance.
Methodology: Double-blind study.
Publications:
Marino M T, Schuster B G, Brueckner R P, Lin E , Kaminskis A , Lasseter K . J Clin Pharmacol.1998;38:227-35.
|
|
