Antidementia drugs-pharmacokinetics

Question 1

Tacrine

Answer 1

short half life and poorly absorbed

metabolised by CYP1A2 enzymes

Question 2

Donepezil

Answer 2

• oral bioavailability around 100% with linear pharmacokinetics
• reaches steady state at 2 weeks
• t 1/2 is 70 hours- enables once daily dosing

Question 3

Rivastigmine

Answer 3

• bioavailability is 40% up to dose of 3mg
• t 1/2 is only 1.5 hrs
• minimal hepatic involvement
• excreted in urine

Question 4

Galantamine

Answer 4

• bioavailability is 905
• low protein binding (18%)
• metabolised by CYP2D6 and CYP3A4
• one third is excreted unchanged in the urine

Question 5

Memantine

Answer 5

low protein binding 45%
long half life 60-80 hours
half the dose of memantine is excreted unchanged in the urine, remainder undergoes hepatic ocnversion to inactive metabolites
-drugs that alkanize the urine reduce the clearance of memantin (e.g carbonic anhydrase inhibitors)