What are the pharmacokinetics of escitalopram (Selective Serotonin Reuptake Inhibitor - SSRI)?

Pharmacokinetics of Escitalopram

Escitalopram demonstrates linear and dose-proportional pharmacokinetics with a long half-life of 27-32 hours, allowing for once-daily dosing and steady-state plasma concentrations achieved within approximately one week of administration. 1, 2

Absorption and Distribution

• Escitalopram is rapidly absorbed from the gastrointestinal tract with maximum plasma concentrations reached within 3-4 hours after oral administration 2
• Food does not affect the absorption of escitalopram 1
• The absolute bioavailability is approximately 80% relative to intravenous administration 1
• Escitalopram has a high volume of distribution (approximately 1100L), indicating extensive tissue distribution 2
• Plasma protein binding is relatively low at 56%, reducing the risk of interactions with highly protein-bound drugs 1, 2

Metabolism

• Escitalopram is primarily metabolized in the liver by cytochrome P450 enzymes, mainly CYP2C19, CYP2D6, and CYP3A4 1, 2
• The main metabolites are:
  • S-demethylcitalopram (S-DCT) - present at approximately one-third the concentration of escitalopram in plasma 1
  • S-didemethylcitalopram (S-DDCT) - typically present at or below quantifiable concentrations 1
• These metabolites have minimal contribution to the therapeutic effect as they are much less potent than escitalopram in inhibiting serotonin reuptake 1, 2
• Escitalopram has negligible inhibitory effects on CYP isoenzymes and P-glycoprotein, suggesting a low potential for drug-drug interactions 2

Elimination

• The mean terminal half-life of escitalopram is approximately 27-32 hours 1, 2
• Oral clearance is approximately 600 mL/min, with about 7% due to renal clearance 1
• Following oral administration, approximately 8% of escitalopram and 10% of S-DCT is recovered in urine 1
• Elimination is primarily through hepatic metabolism 1

Special Populations

• Adolescents: AUC of escitalopram decreased by 19% and Cmax increased by 26% compared to adults, but no dosage adjustment is needed 1
• Elderly (≥65 years): AUC and half-life increased by approximately 50%, with unchanged Cmax, suggesting a reduced dose of 10 mg is appropriate 1
• Hepatic impairment: Oral clearance reduced by 37% and half-life doubled compared to normal subjects; a reduced dose of 10 mg is recommended 1
• Renal impairment: In mild to moderate renal impairment, oral clearance is reduced by 17%, but no dosage adjustment is needed; limited data available for severe renal impairment 1

Clinical Implications

• The linear pharmacokinetics in the 10-30 mg/day dose range allows for predictable dose adjustments 2
• Once-daily dosing is supported by the long half-life 1, 2
• Steady-state concentrations are achieved within 7-10 days 2
• Escitalopram has a favorable pharmacokinetic profile with minimal clinically significant drug interactions 2
• Escitalopram is the S-enantiomer of citalopram and has been shown to be more selective and potent than the racemic mixture 3, 4

Potential Drug Interactions

• Coadministration with CYP3A4 inhibitors like ritonavir does not significantly affect escitalopram pharmacokinetics 2
• Cimetidine and omeprazole can increase escitalopram exposure by 72% and 51% respectively, though these changes are not considered clinically significant 2
• Due to multiple metabolic pathways, clinically relevant drug interactions are minimal compared to other antidepressants 3