Ketoprofen pharmacokinetics and bioavailability based on an improved sensitive and specific assay

Area of Science:

• Pharmacokinetics
• Drug Metabolism and Disposition

Background:

• Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) used for pain and inflammation.
• Understanding ketoprofen's bioavailability and accumulation is crucial for optimizing therapeutic regimens.

Purpose of the Study:

• To compare the bioavailability of ketoprofen from a commercial capsule, a simple capsule, and an aqueous solution.
• To investigate ketoprofen accumulation in plasma following multiple oral doses.

Main Methods:

• A randomized crossover study involving 12 healthy adult males.
• Administration of single oral doses of ketoprofen (50 mg) in three formulations: commercial capsule, simple capsule, and aqueous solution.
• Analysis of plasma ketoprofen concentrations over time to determine pharmacokinetic parameters, including area under the curve (AUC).
• Assessment of ketoprofen accumulation after 13 doses administered every 6 hours.

Main Results:

• Bioavailability of ketoprofen from both commercial (99.7%) and simple (102%) capsules was similar to the aqueous solution.
• Multiple dosing of ketoprofen capsules resulted in a significant 22% increase in AUC compared to a single dose, indicating drug accumulation.
• Peak plasma concentrations were achieved faster with the ketoprofen solution (21 min) compared to capsules (commercial: 72 min; simple: 61 min).
• A two-compartment open model accurately predicted ketoprofen's time-to-peak and clearance (Cl/F = 5.2 L/h).

Conclusions:

• Ketoprofen exhibits comparable bioavailability across different oral formulations.
• Contrary to previous reports, ketoprofen demonstrates accumulation upon multiple dosing, necessitating careful consideration in clinical practice.
• The aqueous solution offers a faster onset of action compared to ketoprofen capsules.