Celexa® (Citalopram Hydrobromide): Structural Formula, Warnings, And Description.pdf

- Structural Formula: Celexa is an SSRI with a unique chemical structure, designated as (±)-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile, HBr. Its molecular formula is C20H22BrFN2O (molecular weight: 405.35).

- Formulations: Available as tablets (10 mg, 20 mg, and 40 mg) and oral solution (2 mg/mL).

- Physical Properties:
- Tablets: Fine, white to off-white powder with inactive ingredients including copolyvidone, corn starch, crosscarmellose sodium, glycerin, lactose monohydrate, magnesium stearate, hypromellose, microcrystalline cellulose, polyethylene glycol, and titanium dioxide.
- Oral Solution: Clear, contains sorbitol, purified water, propylene glycol, methylparaben, natural peppermint flavor, and propylparaben.

- Clinical Pharmacology:

- Pharmacodynamics:
- Acts as a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine (NE) and dopamine (DA) neuronal reuptake.
- Inhibits serotonin (5-HT) uptake primarily through its (S)-enantiomer.
- Has no or low affinity for various receptors, including 5-HT1A, 5-HT2A, dopamine D1/D2, α1/α2-adrenergic, histamine H1, GABA, muscarinic cholinergic, and benzodiazepine receptors.

- Pharmacokinetics:
- Linear and dose-proportional pharmacokinetics with a single or multiple doses (10-60 mg/day).
- Mean terminal half-life of about 35 hours; steady state plasma concentrations achieved within one week.
- Absorbed rapidly after oral administration, reaching peak levels at ~4 hours.
- Bioavailability of ~80% relative to an intravenous dose; not affected by food.
- Volume of distribution (~12 L/kg) and protein binding (80%) are typical for SSRIs.

- Metabolism and Elimination:
- Primarily metabolized by CYP3A4 and CYP2C19, with metabolites contributing minimally to its antidepressant effects.
- Unchanged citalopram is the predominant compound in plasma.

- Population Considerations:
- Elderly subjects have increased AUC and half-life compared to younger ones (up to 50% and 30%, respectively). 20 mg is recommended for most elderly patients.
- Gender differences in AUC observed in some studies, but no significant difference in steady-state serum levels between men and women.