STEADY-STATE PHARMACOKINETICS OF PHENTERMINE EXTENDED-RELEASE CAPSULES

Twenty-one healthy, caucasian, male volunteers completed this randomized single blind, multiple-dose, crossover bioavailability study during which either phentermine HCl capsules (Minobese Forte, reference product) or phentermine base capsules (Duromine, test product) were ingested once daily for 14 days. A washout period of 14 days was allowed between the two treatment phases. On profile days (day 14 of each treatment phase) subjects remained recumbent for 24 hours after drug administration. 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 pharmacokinetic 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 aid of trough plasma phentermine concentrations, it was established that steady-state was reached after 14 days of once daily administration of either product. Adverse events experienced on both treatments included prolonged or recurrent episodes of insomnia, nausea, headache, dry mouth and dizziness. No clinically relevant changes in clinical chemistry or hematology variables occurred during the study.