Uji BA/BE Komparatif dari Formulasi Meloxicam Bermerek & Generik pd Relawan Pria Sehat

Summary

This presentation discusses a bioequivalence study comparing branded and generic Meloxicam formulations in healthy male volunteers. The protocol includes ethical review, randomized crossover design, and single-dose administration, followed by pharmacokinetic analysis of key parameters like Cmax, Tmax, and AUC. The study found no significant differences in the pharmacokinetic profiles of both formulations, confirming their bioequivalence. Additionally, minimal side effects were reported. The research highlights the importance of bioequivalence testing in generics to ensure they offer the same therapeutic benefits as branded drugs without compromising safety.

Takeaways

• 😀 Bioequivalence testing is crucial for ensuring generic drugs have the same bioavailability as branded ones, without compromising safety.
• 😀 The study involves 24 healthy male volunteers, divided into two groups of 12, to compare a generic and a branded meloxicam formulation.
• 😀 The protocol includes 20 key points, such as ethical review, approval from BPOM, and randomization of subjects for unbiased treatment assignment.
• 😀 A single-dose of 15 mg meloxicam is administered during each testing period, with a two-week washout period between doses.
• 😀 Farmakokinetic parameters like Cmax, Tmax, and AUC are used to measure the concentration of meloxicam in plasma, assessing the drug's absorption and distribution.
• 😀 The study is designed as a crossover, single-blind trial, where participants are unaware of the drug they are receiving to avoid bias.
• 😀 Subjects are required to refrain from alcohol or caffeine 48 hours before the drug is administered and must fast for at least 10 hours before the study.
• 😀 Blood samples are taken at specific intervals (0, 0.5, 1, 2, 4, 8, 12, and 24 hours) after administration to measure the drug's plasma concentration.
• 😀 The study finds no significant difference between the branded and generic meloxicam in terms of pharmacokinetic profile, meeting the 80-125% bioequivalence acceptance range.
• 😀 The study does not include urine sampling or dissolution testing due to the nature of meloxicam's action (systemic, highly protein-bound) and the focus on post-marketing clinical evaluation.

Q & A

What is bioequivalence, and why is it important in drug development?

Bioequivalence refers to the condition where two drug products containing the same active ingredient are shown to have equivalent bioavailability. This means that the rate and extent to which the active ingredient is absorbed into the bloodstream are the same for both products. Bioequivalence is crucial in drug development, especially for generic drugs, as it ensures that generics perform in the same way as the branded drugs in terms of efficacy and safety.

What are the primary goals of the bioequivalence testing protocol in the study?

The primary goal of the bioequivalence testing protocol in this study is to evaluate whether the generic formulation of meloxicam is bioequivalent to the branded version. The study aims to compare the pharmacokinetic parameters such as Cmax, Tmax, and AUC to ensure that both formulations have the same rate and extent of absorption in healthy male volunteers.

What does the study design include, and why is a crossover design used?

The study uses a randomized, crossover design with a 2-week washout period between dosing phases. In a crossover design, each subject receives both the generic and branded drugs at different times, allowing for a direct comparison within the same individual. This design reduces variability and helps control for individual differences, providing more reliable results.

How were the subjects selected for this study, and what criteria were used?

The subjects were healthy male volunteers aged 18-50 with a BMI between 19 and 25. They also needed to be non-smokers and free of serious medical conditions. The subjects underwent physical evaluations, including vital signs and medical history checks, to ensure they were fit for participation in the study.

What is the significance of fasting before administering the drug in the study?

Fasting before drug administration is important to control for any variables that could affect the absorption of the drug, such as the influence of food on gastric emptying or drug metabolism. In this study, the subjects were required to fast for at least 10 hours before receiving the meloxicam dose to ensure consistent and accurate pharmacokinetic measurements.

Why was urine sampling not conducted in this study?

Urine sampling was not conducted because the primary focus of the study was on measuring the pharmacokinetics of meloxicam in plasma, not its excretion in urine. Meloxicam is highly bound to plasma proteins (over 99%), making urine sampling less effective or relevant for this specific bioequivalence study.

What methods were used to analyze meloxicam levels in the blood plasma?

The meloxicam concentration in plasma was measured using high-performance liquid chromatography (HPLC). This method provides precise and accurate results, and the study utilized a UV detector to identify and quantify meloxicam at a sensitivity level of 0.005 mg/l.

What are the key pharmacokinetic parameters measured in the study?

The key pharmacokinetic parameters measured in this study include Cmax (maximum concentration), Tmax (time to reach Cmax), and AUC (area under the curve). These parameters help assess how quickly and to what extent meloxicam is absorbed into the bloodstream and how long it remains active in the system.

What were the results of the bioequivalence testing between the generic and branded meloxicam?

The results of the bioequivalence testing showed no significant differences between the generic and branded meloxicam formulations. Both formulations had pharmacokinetic parameters such as AUC and Cmax within the acceptable bioequivalence range of 80-125%, confirming that they are bioequivalent.

Why were certain protocols, such as the repeat testing, not conducted in this study?

Repeat testing was not necessary because the results from the initial tests were consistent and met the required bioequivalence criteria. The design of the crossover study provided a high level of control over individual variability, and the data were reliable, making further testing unnecessary.