STEADY-STATE PHARMACOKINETICS OF PHENTERMINE EXTENDED-RELEASE CAPSULES

Twenty-one healthy, caucasian, male volunteers completed this randomiz ed single blind, multiple-dose, crossover bioavailability study during which either phentermine HCl capsules (Minobese Forte, reference prod uct) or phentermine base capsules (Duromine, test product) were ingest ed once daily for 14 days. A washout period of 14 days was allowed bet ween the two treatment phases. On profile days (day 14 of each treatme nt phase) subjects remained recumbent for 24 hours after drug administ ration. Serial venous blood samples were drawn over the 24 hour dosing interval for plasma phentermine assay by gas chromatography. The 90% confidence intervals for the ''test/reference'' mean ratios of the pha rmacokinetic variables C(max,norm), C(min,norm), AUC(norm) (normalized for difference in the dose of phentermine base), %PTF and T75% C(max) , all fell within the bioequivalence range of 80% to 125%. With the ai d of trough plasma phentermine concentrations, it was established that steady-state was reached after 14 days of once daily administration o f either product. Adverse events experienced on both treatments includ ed prolonged or recurrent episodes of insomnia, nausea, headache, dry mouth and dizziness. No clinically relevant changes in clinical chemis try or hematology variables occurred during the study.