Narcissus and Daffodil

Pharmacology of Narcissus compounds 335
syndrome – drowsiness, disorientation, short-term memory impairment – in ten
healthy volunteers. Although no objective measurements of cognitive function
were made, electro-encephalogram (EEG) monitoring in two subjects showed
changes matching the observed changes in consciousness. Scopolamine replaced
the dominant awake alpha rhythm with slow, disorganised activity; galanthamine
promptly restored the EEG pattern to normal.
PHARMACOKINETICS OF GALANTHAMINE
The reader is referred elsewhere for detailed reviews of the pharmacokinetics of
galanthamine in species other than man (Harvey, 1995; Bores and Kosley, 1996;
Bickel et al., 1991a). Animal data are reported here where they serve to amplify
what is known in man. For a more detailed description of the human data, see
Kewitz (1997).
Galanthamine is commonly administered as the hydrobromide salt, and will be
abbreviated to galanthamine throughout this review, unless other salts were used.
In general, the pharmacokinetics of galanthamine are first-order and linear over a
wide dose range. Table 13.1 contains a summary of values determined for key
pharmacokinetic parameters in man. Galanthamine has been assayed in various
body fluids using a variety of techniques, including high-performance liquid
chromatography (HPLC) and enzyme immunoassay. For details of these, see individual
references.
Table 13.1 Galanthamine pharmacokinetics: summary of human
data a
Parameter Value/comments
Overall kinetics Linear, two-compartment,
first order
Relative oral bioavailability
(from solution or tablets)
85–100%
Time to peak serum level
52–120 min
(Tmax ) after tablets
Absorption half-life (t1/2 abs )
Volume of distribution (Vd)
20 min
1.76–2.90 litre/kg
Distribution half-life (t1/2α) Elimination half-life (t1/2β) Mean serum clearance
6.6–9.6 min
4.4–8.1 h
250–340 ml/h/kg
Mean renal clearance 82–84 ml/h/kg
Galanthamine excreted
unchanged in urine
30–50%
Dose excreted in first 24 hours
Metabolites (see Figure 13.2):
60%
O-demethyl galanthamine (iii) 20% as glucuronide
N-demethyl galanthamine (iv) 5%
Epigalanthamine (v)