CLINICAL PHARMACOKINETICS OF ALPRAZOLAM EXTENDED-RELEASE - A SUMMARY

A new extended-release formulation of alprazolam (alprazolam XR) has b een developed to facilitate less-frequent dosing than is required with the conventional formulation (alprazolam compressed tablet [CT]). Dur ing a study involving chronic dosing of alprazolam XR 6 mg once daily and alprazolam CT 1.5 mg four times daily, the extent of absorption an d peak concentrations were comparable, whereas the trough concentratio n was higher with the latter formulation. During chronic dosing of alp razolam XR 3 mg twice daily and alprazolam CT 1.5 mg four times daily, the extent of absorption, peak concentrations, and trough concentrati ons were comparable. The administration of a high-fat meal in conjunct ion with alprazolam XR I or 3 mg did not affect the extent of absorpti on, but the peak concentration increased by 12% and 26%, respectively. A similar concentration profile was observed when alprazolam XR 3 mg was administered at night as opposed to the morning. Mean maximum seda tion scores on the Nurse Rated Sedation Scale (0-4) are comparable wit h a 3-mg dose of alprazolam XR (2.12 +/- 0.485) and a 1.5-mg dose of a lprazolam CT (2.74 +/- 0.485). During chronic dosing, tolerance to sed ation occurs to the same extent with both formulations. The only diffe rence in pharmacokinetic profiles is the slower absorption of alprazol am XR compared with alprazolam CT. In view of the fact that distributi on, metabolism and elimination are comparable, the half-life and exten t of accumulation during chronic dosing are the same for both formulat ions.