Download Chemical Structure of Donepezil Pharmacokinetics

Donepezil
Donepezil
• Generic name: Donepezil.
• Brand name: Aricept.
• Chemistry: Donepezil hydrochloride is a piperidine
derivative. It is a white crystalline powder with a molecular
weight of 425.96.
• Preparation: 5 and 10 mg tablets.
• Storage: tablets should be stored at room temperature.
• Dosing: Donepezil is generally taken once daily at night
prior to retiring. Its absorption is not affected by food.
Chemical Structure of Donepezil
Pharmacokinetics:
1- Donpezil hydrochloride is a selective, reversible and noncompetitive acetylcholinesterase inhibitor with a relatively high
central versus peripheral specificity.
2- Has extensive extravascular distribution.
3- Highly bound to plasma proteins (95.6%).
4- Given orally, absorbed from the gastrointestinal tract at a
moderate rate. Peak concentration occurring approximately 4 hours
after drug administration.
Pharmacokinetics:
5- Slow clearance from plasma by microsomal hepatic enzymes.
6- Undergoes significant first pass metabolism following oral
administration.
7- Long half-life of approximately 70 hours.
8- 80% of the administered drug is excreted in the urine as unchanged
drug, glucoronidated metabolite and hydrolysis product.
9- Feacal elimination accounts for the remaining 20%.
Mechanism of action:
• AD is characterized by deficits in memory and cognition
that are associated with significant losses of presynaptic
cholinergic function in the brain. Donepezil enhances
cholinergic transmission by reducing the enzymatic
degradation of acetylcholine. Donepezil is 1200 times
more selective for acetylcholinesterase rather than
butylcholinesterase.
Pharmacological effects:
1- It improved cognitive and global function in patients
with mild to moderate AD.
2- It produces no clinically significant changes in
laboratory parameters, including liver function.
3- There is no need to modify the dose in the elderly or in
patients with hepatic or renal failure.
Therapeutic uses:
1- Donepezil gives a short-term improvement in
cognitive function but does not appear to alter the
underlying disease process.
2- Causes a 3-6 month delay in disease progression.
3- Symptomatic improvement of memory, cognition, mood and
behavior.
Drug interactions:
1- Concurrent administration of donepezil with digoxin would
not alter the pharmacokinetic of digoxin.
2- No pharmacodynamic or pharmacokinetic interactions
occur between donepezil and warfarin.
3- The concurrent administration of donepezil and ketoconazole
produce no change in ketoconazole plasma concentrations, but
did result in increase plasma concentrations of donepezil.
4- Donepezil does not alter the pharmacokinetics of
sustained-release theophylline.
Adverse effects:
1- Urinary incontinence.
2- Convulsions.
3- Behavioral worsening.
4- Diarrhea and vomiting.
5- No clinically significant affects on vital signs, hematology or
clinical biochemistry tests.
6- Not associated with hepatotoxicity.
Contraindications:
Not contraindicated in pregnancy, lactation,
hepatic or renal impairment.
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