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Title: No Dosage Adjustments Required When Coadministering Sertraline and Ramelteon: Presented at ACCP

"No Dosage Adjustments Required When Coadministering Sertraline and Ramelteon: Presented at ACCP"

By Maria Bishop BOSTON, MASSACHUSETTS -- September 18, 2006 -- Depressed patients taking the selective serotonin-reuptake inhibitor (SSRI) sertraline may be safely coadministered the chronohypnotic ramelteon to combat insomnia without causing significant decreases in sertraline exposure and vice versa, according to an investigation presenting here at the American College of Clinical Pharmacology 35[^th Annual Meeting (ACCP).

The effects of exposure to multiple doses of the 2 drugs upon each other was not found to be clinically relevant, noted team leader Aziz Karim, PhD, ABCP, vice president of clinical research, Takeda Global Research and Development Center, Lincolnshire, Illinois.

The impetus for the study derived from the fact that, of ramelteon's metabolites (M-I, M-II, M-III and M-IV), the most abundant in human serum is M-II, which also has a fifth to a tenth the binding affinity of ramelteon for the MT1 and MT2 receptors, Dr. Karim noted in his presentation on September 17^th.

Forty-eight healthy subjects (32 male) with a mean age of 30.1 years received open-label ramelteon and/or sertraline under fasting conditions. Serum samples of ramelteon and plasma samples of sertraline were both taken for pharmacokinetic analyses of the drugs and their metabolites. Samples were collected prior to dosing and periodically over 24 hours post-dose. Plasma samples were collected prior to dosing and periodically over 240 (10 days) hours post-dose.

Although the presence of sertraline decreased ramelteon total exposure by 23% and peak exposure by 43%, the investigators noted that this was not considered to be clinically relevant due to ramelteon's highly variable inter-subject pharmacokinetic profile and wide safety margin. Ramelteon was found to have no effect on the systemic availability of sertraline.

Most adverse events in this trial were considered to be mild, with headache being the most common in both treatment groups.

Ramelteon is marketed as Rozerem by Takeda Pharmaceuticals North America.

[Presentation title: Effect of Multiple Oral Doses of Sertraline on the Systemic Availability of Ramelteon, an MT1/MT2-Receptor Agonist. Abstract 120]

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