Comparative Bioavailability of Two Quetiapine Formulations in Healthy Volunteers after a Single Dose Administration

Abstract

The study was performed to compare the bioavailability of two quetiapine 25 mg tablet formulations: the test formulation was quetiapine fumarate (kitapen®) manufactured by Cobalt Pharmaceuticals, Canada/ Arrow Farmacêutica Ltda* (Erowlabs). Seroquel® (quetiapine) from Astrazeneca Brazil was used as reference formulation. The study was conducted open with randomized two period crossover design and one week wash out period in 64 volunteers of both sexes. Plasma samples were obtained over a 48 hour interval. Quetiapine was analyzed by LC-MS-MS in the presence of quetiapine-D8 as internal standard. Plasma samples were obtained over a 48 hour interval. Quetiapine was analyzed by LC-MS-MS in the presence of quetiapine-D8 as internal standard. The mean ratio of parameters Cmax and AUC 0-t and 90% confidence intervals of correspondents were calculated to determine the bioequivalence. The means AUC 0-t for test and reference formulation were 432.41 ng.h/mL and 412.20 ng.h/mL, for AUC 0-∞ were 440.06 ng.h/mL and 418.90 ng.h/mL and, for Cmax 126.94 ng/mL and 108.71 ng/mL, respectively. Geometric mean of quetiapine (kitapen®)/Seroquel® 25 mg individual percent ratio was 97.68% AUC 0-t , 97.47% for AUC 0-∞ and 90.68% for C max. The 90% confidence intervals were 92.67-102.96%, 92.53-102.67%, 83.37-98.64%, respectively. Since the 90% confidence intervals for C max , AUC 0-t and AUC 0-∞ were within the 80-125% interval proposed by Food and Drug Administration, it was concluded that quetiapine (kitapen®) 25 mg tablet was bioequivalent to Seroquel® 25 mg tablet according to both the rate and extent of absorption.

Bioequivalence of two quetiapine extended release tablets in Chinese healthy volunteers under fasting and fed conditions and effects of food on pharmacokinetic profiles

“…Quetiapine was classified as a Biopharmaceutics Classification System (BCS) class II drug, with a low solubility and high permeability, and was absorbed well and quickly after oral administration in humans. Some papers reported the time to the maximum peak plasma concentration (T max ) of quetiapine IR to be 0.6–1.5 hours,1,17,18 while that of quetiapine XR to be 5–6 hours 1,19,20. The elimination half-life (t 1/2 ) of quetiapine was 7–12 hours 17–20.…”

Role of Pharmacokinetic Studies in Drug Discovery

“…This is done by using appropriate statistical methods for data analysis and adequate sample size [57]. In a study with a sufficient amount of data, mean values, variance, and confidence intervals of drug concentrations and pharmacokinetic parameters should be estimated using appropriate statistical methods [58][59][60]. Major variables such as drug concentrations and pharmacokinetic parameters should be analyzed based on their statistical properties of distribution, and data transformation such as logarithmic transformation should be performed whenever necessary.…”

Analysis of Pharmacokinetic & Pharmacodynamic Models in Oral and Transdermal Dosage Forms

“…Quetiapine is indicated for the treatment of schizophrenia and bipolar disorder. Quetiapine is metabolized by the liver [3].…”

“…It is a pharmacokinetic term that describes the rate and extent to which the drug ingredient is absorbed from a drug product and becomes available in the systemic circulation [2]. Bioavailability is also a pharmaceutical form refers to the extent and speed of absorption of the active principle contained in it [3]. But studies assess the relative fraction of the orally administered dose that is absorbed into the systemic circulation when compared to the bioavailability data for a solution, suspension, or intravenous dosage form and provide pharmacokinetic information related to distribution, elimination, effects of nutrients on absorption of the drug, dose proportionality, linearity in pharmacokinetics of the active moieties and appropriate inactive moieties [4].…”