Pharmacokinetics of Galanthamine (A Long-Acting Anticholinesterase Drug) in Anaesthetized Patients

Abstract

The pharmacokinetics of the long-acting anticholinesterase drug, galanthamine, were investigated in eight patients. After i.v. injection of 0.3 mg kg-1, the decrease in the serum concentration of galanthamine followed a biexponential curve. The serum concentration decreased rapidly from 543 +/- 47 ng ml-1 to 128 +/- 14 ng ml-1 between 2 and 30 min with a T1/2 alpha of 6.42 +/- 2.15 min, and then declined more slowly with a T1/2 beta of 264 +/- 28 min. Total serum clearance of galanthamine amounted to 5.37 +/- 0.87 ml min-1 kg-1, and the renal clearance was 1.36 +/- 0.10 ml min-1 kg-1. The cumulative urinary excretion of galanthamine between 0 and 48 h after injection amounted to 28.0 +/- 5.4% of the administered dose. The biliary excretion of galanthamine during 24 h amounted to 0.2 +/- 0.1% of the dose. There was no evidence of glucuronide or sulphate conjugation of galanthamine.

Pharmacokinetics of Galanthamine Hydrobromide after Single Subcutaneous and Oral Dosage in Humans

“…Recently, galanthamine pharmacokinetics and metabolism in labora tory animals were investigated [7][8][9][10]]. An earlier paper described its pharmacokinetics in surgical patients [11], but a systematic knowledge on its pharmacokinetics in man is still not available.…”

The Metabolism and Excretion of Galantamine in Rats, Dogs, and Humans

“…Although earlier studies have been published on the pharmacokinetic profile of galantamine in both animals (Mihailova et al, 1985;Mihailova and Yamboliev, 1986;Bickel et al, 1991a) and humans (Westra et al, 1986;Mihailova et al, 1989;Bickel et al, 1991b), advances in analytical techniques have made further elucidation of the metabolic profile of this compound possible. The studies presented here were therefore performed to elucidate the metabolic profile of galantamine after oral dosing and to compare the metabolism and excretion of galantamine in rats, dogs, and humans.…”

Galanthamine Hydrobromide in a Long-Term Treatment of Alzheimer's Disease

“…GAL has been shown to be a long-act ing agent in anaesthetized patients [13], but no clinical trials on the treatment of Alzheimer's disease have been published so far.…”

“…They were thus highly predictable, which is an important advantage over physostigmine and tacrine, whose pharmacokinetics are non linear [26][27][28]. The plasma half-life of GAL in humans was previously mea sured in anaesthetized patients [13] but not in conscious subjects. Our preliminary data from the patient and the volunteer confirm the half-life to be markedly longer than with physostigmine or tacrine.…”

“…Since that time, it has been used safely as an anticurare agent in anaesthesia [11][12][13]; it was also applied for var ious neurologic disorders [14] in more than 100 patients for several weeks. Its inhibitory effects on cholinester ases have been described by Irwin and Smith [ 15], Schuh [16] and recently by Thomsen and Kewitz [17].…”