What is the elimination half-life of amlodipine and how long does it take to be completely eliminated from the body?

Amlodipine Elimination Time from the Body

Amlodipine has a long terminal elimination half-life of 30-50 hours, requiring approximately 5-7 days (5-7 half-lives) for complete elimination from the body after discontinuation. 1

Pharmacokinetic Profile of Amlodipine

Half-life and Elimination

• Amlodipine exhibits a biphasic elimination pattern with a terminal elimination half-life of approximately 30-50 hours 1
• Complete elimination of a drug typically takes 5-7 half-lives, meaning amlodipine requires 5-7 days (150-350 hours) to be fully cleared from the system 1, 2
• Steady-state plasma levels are reached after 7-8 days of consecutive daily dosing, reflecting this long elimination period 1

Metabolism and Excretion

• Amlodipine is extensively metabolized in the liver (about 90% converted to inactive metabolites) 1
• Approximately 10% of the parent compound and 60% of metabolites are excreted in urine 1
• The drug is highly protein-bound (93% bound to plasma proteins in hypertensive patients) 1, 3

Factors Affecting Elimination Time

Patient-Specific Factors

• Age: Elderly patients have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40-60% 1
• Hepatic function: Patients with hepatic insufficiency have decreased clearance and longer elimination times 1
  • The plasma elimination half-life is extended to approximately 56 hours in patients with impaired hepatic function 1
• Heart failure: Patients with moderate to severe heart failure show increased AUC similar to elderly patients 1

Renal Function

• The pharmacokinetics of amlodipine are not significantly influenced by renal impairment 1
• Patients with renal failure may receive the usual initial dose without adjustment for elimination concerns 1

Clinical Implications of Amlodipine's Long Half-Life

Persistent Antihypertensive Effect

• The long elimination half-life contributes to a prolonged antihypertensive effect that extends beyond 24 hours 4
• Research has shown that blood pressure does not significantly increase even after 3 days of medication discontinuation 4
• This extended duration of action provides a buffer against missed doses, maintaining blood pressure control 2, 4

Adherence Testing Considerations

• In chemical adherence testing for hypertension medications, amlodipine's slow clearance means it can be analytically positive up to a week after the last ingestion 5
• This characteristic can make it difficult to distinguish between regular and sporadic dosing in adherence monitoring 5

Drug Interactions During Elimination Period

• As a CYP3A substrate, strong CYP3A inhibitors may increase amlodipine plasma concentrations and potentially extend elimination time 1
• Amlodipine itself is a weak inhibitor of CYP3A and may affect the elimination of other drugs metabolized by this pathway 1

Practical Considerations

Discontinuation Protocol

• Due to the gradual elimination, abrupt discontinuation of amlodipine does not typically cause rebound hypertension 2
• When switching to another antihypertensive medication, the persistent effect of amlodipine should be considered during the transition period 4

Monitoring After Discontinuation

• Blood pressure monitoring should continue for at least 5-7 days after discontinuation to ensure proper transition to alternative therapy if needed 2, 4
• The gradual offset of action helps prevent acute blood pressure fluctuations during medication changes 6