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The Pharmacokinetics of Escitalopram After Oral and Intravenous Administration of Single and Multiple Doses to Healthy Subjects

From the Department of Clinical Pharmacology and Pharmacokinetics, H. Lundbeck A/S, Copenhagen, Denmark (B. Søgaard, H. Mengel, F. Larsen); and the Forest Research Institute, Forest Laboratories, Inc, Jersey City, New Jersey (N. Rao).

The pharmacokinetics of escitalopram (S-citalopram) and its principal metabolite, S-demethylcitalopram (S-DCT), were investigated after intravenous and oral administration to healthy subjects. After intravenous infusion of escitalopram, the mean systemic clearance and volume of distribution were 31 L/h and 1100 L, respectively. After oral administration of single or multiple doses, the absorption was relatively fast, with the maximum observed plasma or serum concentration (C_max) attained after 3 to 4 hours. The mean half-lives were 27 and 33 hours, respectively; steady state was attained within 10 days. The area under the plasma or serum concentrationtime curve from time zero to 24 hours and C_max was both linear and proportional to the dose. The apparent volume of distribution was around 20 L/kg. Comparison of the systemic and oral clearance implied a high absolute bioavailability. There was no evidence of interconversion from S-citalopram to R-citalopram either in plasma or in urine. Concurrent intake of food had no effect on the pharmacokinetics of escitalopram or its metabolite. All treatments were well tolerated.

Key Words: Escitalopram • citalopram • enantiomer • healthy volunteers • single dose • multiple dose • cross-over • pharmacokinetics • bioequivalence • tolerability

Address for reprints: B. Søgaard, Department of Clinical Pharmacology, H. Lundbeck A/S, Ottiliavej 7, DK-2500 Copenhagen-Valby, Denmark.

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