Evaluation of Pharmacokinetics and Safety With Bioequivalence of Anastrozole in Healthy Chinese Volunteers: Bioequivalence Study Findings

Abstract

Anastrozole is a third-generation aromatase inhibitor that exerts potent anti-breast cancer effects. This trial aimed to explore the pharmacokinetics (PK) and safety with bioequivalence of orally administered anastrozole provided by 2 sponsors in healthy volunteers.Two separate open-label, randomized, single-dose, crossover-design studies consisting of a fasting study (n = 23) and a fed study (n = 23, 1 participant withdrew before taking medication) were conducted. In each study, healthy volunteers were randomized to receive the test product (Haizheng Pharmaceutical Group) followed by the reference drug (AstraZeneca Pharmaceuticals LP), or vice versa. Each study subject received a 1-mg anastrozole tablet with a 21-day washout. The plasma concentrations of anastrozole were measured with liquid chromatographytandem mass spectrometry, and PK parameters were determined by noncompartmental analysis. Forty-six healthy female volunteers were enrolled. For patients enrolled in the fasting study, the mean age was 55.0 years, mean weight was 57.1 kg, mean body mass index was 23.6 kg/m 2 , and mean height was 155.5 cm. For patients enrolled in the fed study, the mean age was 54.2 years,mean weight was 55.9 kg,mean body mass index was 23.9 kg/m 2 , and mean height was 152.8 cm.All PK end points met the predefined criteria for PK equivalence. In fasting subjects, the median maximum plasma concentration was 23.4 and 22.6 at 1 hour for test and reference formulations, respectively. The maximum plasma concentration in fed subjects was 18.7 and 18.5 at 4 hours for test and reference formulations, respectively. Both fasting and fed studies achieved plausible bioequivalence. Anastrozole was well tolerated and exhibited a favorable safety profile at the prescribed doses. The severity of observed adverse events assessed according to the Common Terminology Criteria for Adverse Events (version CTCAE4.03) was mild, and some of the adverse events were not caused by anastrozole. Furthermore, the results of our study under fasting and fed conditions demonstrated bioequivalence of the test and reference products.

Electrochemical Oxidation of Anastrozole over a BDD Electrode: Role of Operating Parameters and Water Matrix

“…Anastrozole (ANZ), whose main features are shown in Table 1, is a third-generation nonsteroidal drug that can potentially decrease global deaths due to breast cancer [3]. Available on the market since 1995 and approved by 79 countries, ANZ is on the WHO's list of Essential Medicines [4,5]. It is categorized as a non-steroidal benzotriazole, available in the form of oral tablets [6].…”

“…With over 3 million prescriptions of ANZ handed out in 2020 in the US alone, it is a readily available drug [7]. ANZ is absorbed by the body, metabolized, and excreted out by the kidneys through urine with more than 10% of the drug intact [4,8]; thus, this drug and its metabolites enter the water streams.…”