PMID- 11936568
OWN - NLM
STAT- MEDLINE
DCOM- 20021011
LR  - 20131211
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 42
IP  - 4
DP  - 2002 Apr
TI  - Pharmacokinetics and safety of galantamine in subjects with hepatic impairment 
      and healthy volunteers.
PG  - 428-36
AB  - The objective of this study was to compare the pharmacokinetics and safety of 
      galantamine in subjects with hepatic impairment with those in healthy subjects. 
      This was an open-label study in which a single oral 4-mg dose of galantamine was 
      administered to volunteers with mild (Child-Pugh score of 5-6, n = 8), moderate 
      (Child-Pugh score of 7-9, n = 8), or severe hepatic impairment (Child-Pugh score 
      of 10-15, n = 1) and to healthy, matched control subjects (n = 8). Galantamine 
      pharmacokinetics and safety (adverse events, laboratory test results, 
      electrocardiograms, vital signs, and cardiac events) were assessed over 6 days 
      after administration of galantamine. The pharmacokinetic parameters of 
      galantamine were similar in subjects with mild hepatic impairment compared with 
      healthy controls. Compared with the healthy control group, subjects with moderate 
      hepatic impairment showed relative increases in the area under the 
      plasma-concentration curve from zero to infinity (AUC0-infinity) (+33%) and 
      terminal half-life (t1/2) (+30%) (p = 0.051 and p = 0.003, respectively), a 23% 
      relative decrease in total plasma clearance (p = 0.061), and a small but 
      significant relative increase in the fraction of free plasma galantamine (p = 
      0.009). Galantamine was well tolerated by all subjects. There were no serious 
      adverse events (AEs) or premature withdrawals from the study because of AEs. 
      Reported AEs were headache (three cases), nausea (one case), and paresthesia (one 
      case). There were no clinically relevant changes in clinical laboratory findings, 
      vital signs, and electrocardiograms. Low patient recruitment (n = 1) precluded 
      statistical analysis of galantamine pharmacokinetics and safety in severe hepatic 
      impairment. It was concluded that the pharmacokinetics of galantamine in subjects 
      with mild hepatic impairment was similarto those in healthy subjects. In subjects 
      with moderate hepatic impairment, galantamine clearance was decreased by 
      approximately 23% compared with normal volunteers. Galantamine was also well 
      tolerated and appeared to be safe in subjects with mild ormoderate hepatic 
      impairment. Based on the study results, it appears that it would not be necessary 
      to adjust doses of galantamine during administration to subjects with mild 
      hepatic impairment. In subjects with moderately impaired hepatic function, dose 
      titration should proceed cautiously. Unfortunately, difficulties with patient 
      recruitment did not allow adequate assessment of the safety of galantamine in 
      subjects with severe hepatic impairment in this study. Therefore, the use of 
      galantamine in subjects with severe hepatic impairment is not recommended.
FAU - Zhao, Qinying
AU  - Zhao Q
AD  - Johnson & Johnson Pharmaceutical Research and Development, LLC, Titusville, New 
      Jersey 08560-0200, USA.
FAU - Iyer, Ganesh R
AU  - Iyer GR
FAU - Verhaeghe, Tom
AU  - Verhaeghe T
FAU - Truyen, Luc
AU  - Truyen L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0D3Q044KCA (Galantamine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alzheimer Disease/drug therapy/metabolism
MH  - Analysis of Variance
MH  - Area Under Curve
MH  - Cholinesterase Inhibitors/adverse effects/pharmacokinetics/therapeutic use
MH  - Female
MH  - Galantamine/*adverse effects/*pharmacokinetics/therapeutic use
MH  - Humans
MH  - Liver Diseases/*drug therapy/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Protein Binding/physiology
MH  - Statistics, Nonparametric
EDAT- 2002/04/09 10:00
MHDA- 2002/10/12 04:00
CRDT- 2002/04/09 10:00
PHST- 2002/04/09 10:00 [pubmed]
PHST- 2002/10/12 04:00 [medline]
PHST- 2002/04/09 10:00 [entrez]
PST - ppublish
SO  - J Clin Pharmacol. 2002 Apr;42(4):428-36.