Appendix A
PYRIDOSTIGMINE PHARMACOKINETIC DATA
Table A.1
Pyridostigmine Pharmacokinetic Data
Characteristic
Onset of action
after oral
administration
Onset (time to
initial detection
in blood)
Duration of action
after oral
administration
Intravenous
elimination halflife
Value
Species
30–45 min
Human
McEnvoy, 1991
30 min
Human
Whinnery, 1984
3–6 hr
Human
McEnvoy, 1991
30 min
Human
(“clinical
results”)
Human
Lietman, 1993
97 min
1.9 hrs
Oral elimination
half-life
Bioavailability
Mean concentration at which
50% of the red
blood cell AChE
activity was
inhibited (IC50)
200 min
Human
3.7±1.0 hours
Human
1.78±0.24 hr
Human
7.6±2.4%
14%
29%
31.8 ng/ml
Human
Human
Human
Human
287
Source
Breyer-Pfaff, 1985
Sidell, 1990, based on Cronnelly, 1980;
Breyer-Pfaff, 1985; Kornhauser, 1988
Breyer-Pfaff, 1985
Sidell, 1990, based on Cronnelly, 1980;
Breyer-Pfaff, 1985; Kornhauser, 1988
Whinnery, 1984, citing Eur J Clin Pharm,
423–428, 1980
Whinnery, 1984
Breyer-Pfaff, 1985
Kornhauser, 1988
Lietman, 1993
288 Pyridostigmine Bromide
Table A.1—continued
Characteristic
Value
Species
Source
Time to peak
plasma
concentration,
fasting
Time to peak
plasma level after
oral dosing
Time to peak
plasma
concentration,
with food
Plasma clearance
1.7 hr
Human
Whinnery, 1984
1.5–2.5 hrs
Human?
Kolka, 1991, citing Aquilonius 1980
3.2 hr
Human
Whinnery, 1984
44.62L/hr or
744 ml/min
0.66±0.22
l/kga hr
8–10 hours
Human
Lietman, 1993
Human
Whinnery, 1984
Human
Kolka, 1991, citing Aquilonius 1980
8.5 (SD 8.7)
(ml/min/kg)
1.1 (SD 0.3)
L/kg
1.365/hr
Human
Sidell, 1990, based on Cronnelly, 1980;
Breyer-Pfaff, 1985; Kornhauser, 1988
Sidell, 1990, based on Cronnelly, 1980;
Breyer-Pfaff, 1985; Kornhauser, 1988
Lietman, 1993
Time at which 95%
of the drug is
eliminated
Total clearance
Volume of
distribution
Mean rate constant of
elimination
Urinary excretion
Human
Human
80–90%
(SD 0.3)
Sidell, 1990, based on Cronnelly, 1980;
Breyer-Pfaff, 1985; Kornhauser, 1988
a Whinnery: from 5 males given 120 mg PB orally.
Table A.2
Animal Data
Characteristic
Value
Species
Urinary Excretion
90%
rat
Metabolite, 3-hydroxy-N-methylpyridium, as
fraction of excreted dose
Plasma elimination half life (iv)
1/3
rat
19 min
rat
Source
Yamamoto, Sawada, et
al., 1995
Yamamoto, Sawada, et
al., 1995
Yamamoto, Sawada, et
al., 1995
Additional information derived from rats:
•
No dose dependence in pharmacokinetic behavior in the range of 0.5–2
µmol/kg of PB in rats (Yamamoto, Sawada, et al., 1995).
Pharmacokinetic Data 289
•
Elimination: role of liver and kidneys. Contrary to rapid elimination, high
accumulations are found in liver and kidney. Tissue: plasma partition
coefficients (Kp) of cholinesterase inhibitors are about eight for liver and 15
for kidney at 20 minutes, suggesting these must be concentratively uphill
transported into these tissues like other quaternary ammonium compounds. Though about 50 percent of the dose is distributed into liver and
kidney at 20 minutes after intravenous administration, distribution volumes at steady state are relatively small—0.3–0.7 l/kg—larger than the
extracellular space and similar to the muscle/plasma concentration ratio.
Once in the liver and kidney, PB may not be able to return to plasma
compartment; uptake to these tissues may be regarded as an elimination
process, and uptake to liver and kidneys may be the major determinant of
total body clearance (Yamamoto, Sawada, et al., 1995).