Appendix A

Pyridostigmine Pharmacokinetic Data

Table A.1
Pyridostigmine Pharmacokinetic Data

Characteristic Value Species Source
Onset of action after oral administration 30-45 min Human McEnvoy, 1991
Onset (time to initial detection in blood) 30 min Human Whinnery, 1984
Duration of action after oral administration 3-6 hr Human McEnvoy, 1991
Intravenous elimination half-life 30 min Human ("clinical results") Lietman, 1993
97 min Human Breyer-Pfaff, 1985
1.9 hrs Sidell, 1990, based on Cronnelly, 1980; Breyer-Pfaff, 1985; Kornhauser, 1988
Oral elimination half-life 200 min Human Breyer-Pfaff, 1985
3.7±1.0 hours Human Sidell, 1990, based on Cronnelly, 1980; Breyer-Pfaff, 1985; Kornhauser, 1988
1.78±0.24 hr Human Whinnery, 1984, citing Eur J Clin Pharm, 423-428, 1980
Bioavailability 7.6±2.4% 14% 29% Human Human Human Whinnery, 1984 Breyer-Pfaff, 1985 Kornhauser, 1988
Mean concentration at which 50% of the red blood cell AChE activity was inhibited (IC50) 31.8 ng/ml Human Lietman, 1993
Characteristic Value Species Source
Time to peak plasma concentration, fasting 1.7 hr Human Whinnery, 1984
Time to peak plasma level after oral dosing 1.5-2.5 hrs Human? Kolka, 1991, citing Aquilonius 1980
Time to peak plasma concentration, with food 3.2 hr Human Whinnery, 1984
Plasma clearance 44.62L/hr or 744 ml/min Human Lietman, 1993
0.66±0.22 l/kgahr Human Whinnery, 1984
Time at which 95% of the drug is eliminated 8-10 hours Human Kolka, 1991, citing Aquilonius 1980
Total clearance 8.5 (SD 8.7) (ml/min/kg) Human Sidell, 1990, based on Cronnelly, 1980; Breyer-Pfaff, 1985; Kornhauser, 1988
Volume of distribution 1.1 (SD 0.3) L/kg Human Sidell, 1990, based on Cronnelly, 1980; Breyer-Pfaff, 1985; Kornhauser, 1988
Mean rate constant of elimination 1.365/hr Human Lietman, 1993
Urinary excretion 80-90% (SD 0.3) Sidell, 1990, based on Cronnelly, 1980; Breyer-Pfaff, 1985; Kornhauser, 1988

aWhinnery: from 5 males given 120 mg PB orally.

Table A.2
Animal Data

Characteristic

Value

Species

Source

Urinary Excretion

90%

rat

Yamamoto, Sawada, et al., 1995

Metabolite, 3-hydroxy-N-methylpyridium, as fraction of excreted dose

1/3

rat

Yamamoto, Sawada, et al., 1995

Plasma elimination half life (iv)

19 min

rat

Yamamoto, Sawada, et al., 1995

Additional information derived from rats:


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