Absolute bioavailability, pharmacokinetics, renal and biliary clearance of distigmine after a single oral dose in comparison to i.v. administration of 14C-distigmine-bromide in healthy volunteers.
OBJECTIVE
The aim of the study was to determine the absolute bioavailability and pharmacokinetics after a single dose oral administration in comparison to i.v. administration of 14C-labelled distigmine-bromide (14C-Ubretid) in healthy male volunteers.


RESULTS
After the intravenous administration, distigmine is eliminated from the body by renal excretion (85%), and for a small fraction by biliary excretion in the feces (4%). This situation is reversed after an oral administration, where 6.5% of the dose is recovered from the urine and 88% from the feces. This means that distigmine after oral administration is hardly absorbed, the calculated bioavailability is 4.65%.


CONCLUSIONS
The mean absorption time (MAT) after oral administration was 10 h, influencing the t(1/2alpha) (1.4 vs 4.5 h) and the t(1/2beta) (60 vs 70 h) to higher values than after the i.v. administration (p < 0.05).
Vree
T B
TB
Institute of Anesthesiology, Academic Hospital Nijmegen, The Netherlands.
Waitzinger
J
J
Hammermaier
A
A
Radhofer-Welte
S
S
D000042:Absorption; D000284:Administration, Oral; D001659:Biliary Tract / Q000378:metabolism*; D001682:Biological Availability; D002250:Carbon Radioisotopes; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011726:Pyridinium Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D002800:Cholinesterase Inhibitors; D011726:Pyridinium Compounds; C084645:distigmine