Pharmacokinetic profile of the extended-release formulation of quetiapine fumarate (quetiapine XR): clinical implications

OBJECTIVES: A series of studies were conducted to guide the development and characterise the pharmacokinetics of extended-release quetiapine fumarate (quetiapine XR), a once-daily formulation to control the release of the drug. METHODS: Data from these studies are described and discussed herein. RESULTS: Once-daily quetiapine XR produced a similar area under the plasma concentration-time curve (AUC), minimum plasma concentration (Cmin) and a slightly lower maximum plasma concentration (Cmax) than the equivalent dose of immediate-release quetiapine (quetiapine IR) given twice daily. In a crossover, head-to-head study, total daily exposure, measured by AUC at steady state, was less variable with quetiapine XR versus quetiapine IR (percent coefficient of variation 39.2% versus 51.2%, respectively). Compared with fasting, a high-fat meal increased the AUC and Cmax for quetiapine XR, whereas a light meal had no significant effect on these parameters. Quetiapine XR exhibits a less pronounced D2 receptor occupancy peak and receptor occupancy levels remain higher for longer compared with quetiapine IR. Quetiapine XR was generally well tolerated with a safety profile similar to quetiapine IR, although the intensity of sedation in the first hours of treatment was significantly lower (p < 0.01) with quetiapine XR versus IR. CONCLUSION: At steady state, quetiapine XR provided a similar AUC and Cmin and a slightly lower Cmax relative to an equivalent dose of quetiapine IR administered twice daily. Quetiapine XR exhibited linear pharmacokinetics in the dose range tested and no food effect was observed with a light meal. Once-daily dosing and simpler dose titration makes using quetiapine XR convenient for clinicians and patients. Quetiapine XR has predictable pharmacokinetics and was generally well tolerated, with significantly lower intensity of sedation after the first hours of administration compared with quetiapine IR. With once-daily quetiapine XR, the impact of daytime sedation may be mitigated by evening dosing.