Trazodone conventional and controlled-release formulations: pharmacodynamic effects after single and repeated administration.
In a double-blind study, the pharmacodynamic effects of single and repeated doses of two formulations of trazodone were compared in 14 healthy young volunteers (6 men and 8 women). They received either 100 mg trazodone conventional capsules or 150 mg controlled-release tablets daily at 08.00 hours for two 7-day periods separated by a 'wash-out' period of 2 weeks. Blood pressure standing and lying, critical flicker fusion frequency and manual dexterity were measured on Days 1 and 7 of each session before and at intervals up to 8 hours after the dose. Manual dexterity was tested by measuring the time taken to drop 50 airgun pellets down a narrow tube. A daily pre-dose blood sample was also taken for measurement of trazodone to check compliance and to confirm that steady state had been achieved. Steady state plasma concentrations were reached by Day 2 of repeated dosing on both treatments. There was a trend towards shorter duration of the expected depressant effect of trazodone on critical flicker fusion frequency and manual dexterity on Day 7 for both treatments, which was significantly different between treatments for manual dexterity (p less than 0.001): for the controlled-release tablet, manual dexterity performance was better on Day 7 than on Day 1 at all times after dosing, whereas for the conventional capsule manual dexterity was worse on Day 7 than on Day 1 until 4 and 8 hours after dosing, when performance was better than on Day 1. In this study, both formulations of trazodone caused the expected negative effects on psychomotor function. Further studies would be required to confirm the apparent advantage of the controlled-release tablet in the test of manual dexterity.
Debbas
N M
NM
Charterhouse Clinical Research Unit Limited, London, England.
Ankier
S I
SI
Warrington
S J
SJ
D000328:Adult; D000704:Analysis of Variance; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D014196:Trazodone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D014196:Trazodone