Steady-state bioequivalence 2-way crossover study of two quetiapine prolonged-release 400 mg tablet formulations in normal male and female healthy subjects under fasting conditions
| Autor: | Magdalene Kalovidouris, Fethi Trabelsi, Martha Nikolaidou, Negar Gharavi |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Cmax Bioequivalence Quetiapine Fumarate Young Adult Cmin Pharmacokinetics Tandem Mass Spectrometry Drugs Generic Humans Medicine Pharmacology (medical) Chromatography High Pressure Liquid Pharmacology Cross-Over Studies business.industry Fasting Middle Aged Crossover study Confidence interval Therapeutic Equivalency Area Under Curve Delayed-Action Preparations Anesthesia Quetiapine Female business Antipsychotic Agents Tablets medicine.drug |
| Zdroj: | Int. Journal of Clinical Pharmacology and Therapeutics. 54:732-742 |
| ISSN: | 0946-1965 |
| DOI: | 10.5414/cp202609 |
| Popis: | Objective The purpose of this study was to assess bioequivalence between a generic and a brand quetiapine 400 mg prolonged-release (PR) formulation (Pharmathen S.A.; AstraZeneca Seroquel Prolong® Methods Randomized, open-label, steady-state, 2-way crossover design in 48 subjects under fasting conditions. As a quetiapine dose of 400 mg was suspected to be high when administered to healthy subjects, we proceeded with an innovative design where subjects were titrated up using 150 mg, 200 mg, and 300 mg daily doses; first treatment (days 4 - 9) and second treatment (days 10 - 15), and then a tapering down phase (days 16 - 17). Blood samples were collected in EDTA K2 τ, Cmax, and Cmin. ANOVA was performed on the ln-transformed data and 90% confidence interval (90% CI) was determined. Bioequivalence was concluded if the 90% CI of AUCτ, Cmin, and Cmax fell within 80.00 - 125.00%. Results 46 volunteers completed the study and were included in the analyses. Arithmetic mean (SD) for AUCτ were 7,161.18 (3,687.10) ng×h/mL and 7,184.27 (3,304.29) ng×h/mL, Cmax were 595.61 (345.98) ng/mL and 597.06 (253.67) ng/mL, and Cmin were 119.47 (84.24) ng/mL and 124.22 (137.68) ng/mL, respectively, for the test and reference. All pharmacokinetic parameters met the acceptance criteria as the 90% CI felt within 95.98 - 104.21%, 91.48 - 105.89%, and 86.32 - 104.49% for AUCτ, Cmax, and Cmin, respectively. Both formulations were well tolerated and no serious adverse events were reported. Conclusion Our innovative design allowed safe administration of quetiapine 400 mg PR daily doses to healthy volunteers. Both Pharmathen and AstraZeneca formulations were well tolerated and bioequivalent under steady-state conditions. . |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|