Bioavailability and Bioequivalence

Bioavailability (BA) is the extent and rate to which the active drug ingredient or active moiety from the drug product is absorbed and becomes available at the site of drug action. Assessing BA early in the drug discovery process reduces attrition rates and guides subsequent drug development processes. As a critical indicator of drug absorption, BA is determined by comparing the pharmacokinetic (PK) measurements of the drug target in the systemic system following extravascular dosing or intravenous dosing.

Bioequivalence (BE) studies are often carried out between two drugs or drug formulations to compare their bioavailability (BA). BE is achieved when similar BAs are attained after administering the test and reference drugs/formulations at the same molar dose under similar conditions in an appropriately designed study. Therefore, BE is an essential component in demonstrating therapeutic equivalence and is a prerequisite to the approval of generic drug products or new drug formulations.

Creative Bioarray provides professional pharmacokinetic testing services to help customers determine the bioavailability and bioequivalence of drugs.

Animal species

Rodents

Mice, Rats, Guinea pigs

Non-rodents

Dogs, Minipigs, Non-human primates

Study Design

Bioavailability

The study is typically divided into different groups based on the selected dosing methods, with the most widely used intravenous (iv) injection and oral administration (po). A standard study investigating the oral BA of a drug compound in rats is as follows.

Figure 1. Standard study investigation of oral BA of a drug.

Bioequivalence

A conventional BE study design is a single-dose, two-treatment, crossover, in vivo experiment with pharmacokinetic (PK) endpoints. A typical BE study investigating the oral BE of two drug formulations in rats is as follows.

Figure 2. Standard study investigation of the oral BE of two drug formulations.

According to different research purposes, our experimental design can be adjusted in the following aspects, such as

Additional animals
Custom timepoints
Parallel non-crossover designs
Higher-order crossover designs
Fed/food effects
Sample size calculation

Drug dosing routes

Default: oral administration (po)
Others: intravenous (iv), intraperitoneal (ip), intramuscular (im), and subcutaneous (sc) injections, iv cannulation

Drug dosage

While a single dose for each drug/formulation is usually given to each animal, other drug dosing methods can be included to accommodate your specific needs.

Additional dosage groups
Vehicle dosing
Repeated dosage after washout in the same animal
Multiple-dose studies for studying steady-state exposure
Sample collection
Serial sampling
Terminal blood sampling
Additional or custom time points to cover the exposure period of test compound
Tissues or biological fluids collection for tissue distribution analysis

Endpoints

LC-MS/MS measures the concentrations of test compounds in plasma to generate a concentration-time profile for each dosing group, based on PK parameters—including C_max, T_max, AUC_0-t, AUC_∞, BA, K_e, t_1/2, C₀, V_d, and CL—are calculated using non-compartmental analysis.

BE evaluation is then performed after logarithmic transformations of the PK parameters (C_max, AUC_0-t, AUC_∞). For each PK parameter, BE is assessed by calculating standard 90% confidence intervals (CIs) of the geometric mean ratios between the test and reference drugs/formulations. Average BE is claimed if 90% CIs for these parameters fall within 80 ± 125% (log 0.8–1.25).

Quotation and Ordering

As with all of our in vivo services, we ensure to keep in contact during studies. If you have any special needs or questions regarding our services, please feel free to contact us to support our experienced experts. We look forward to working with you in the future.

Reference

FDA Guidance for Industry. Safety Testing of Drug Metabolites. (March 2020)

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