Albumin Supplement Affects the Metabolism and Metabolism-Related Drug-Drug Interaction of Fenoprofen Enantiomers.

The influence of albumin towards the metabolism behavior of fenoprofen enantiomers and relevant drug-drug interaction was investigated in the present study. The metabolic behavior of fenoprofen enantiomers was compared in a phase II metabolic incubation system with and without bovine serum albumin (BSA). BSA supplement increased the binding affinity parameter (Km) of (R)-fenoprofen towards human liver microsomes (HLMs) from 148.3 to 214.4 µM. In contrast, BSA supplement decreased the Km of (S)-fenoprofen towards HLMs from 218.2 to 123.5 µM. For maximum reaction velocity (Vmax), the addition of BSA increased the Vmax of (R)-fenoprofen from 1.3 to 1.6 nmol/min/mg protein. In the contrast, BSA supplement decreased the Vmax value from 3.3 to 1.5 nmol/min/mg protein. Andrographolide-fenoprofen interaction was used as an example to investigate the influence of BSA supplement towards fenoprofen-relevant drug-drug interaction. The addition of 0.2% BSA in the incubation system significantly decreased the inhibition potential of andrographolide towards (R)-fenoprofen metabolism (P < 0.001). Different from (R)-fenoprofen, the addition of BSA significantly increased the inhibition potential of andrographolide towards the metabolism of (S)-fenoprofen. BSA supplement also changed the inhibition kinetic type and parameter of andrographolide towards the metabolism of (S)-fenoprofen. In conclusion, albumin supplement changes the metabolic behavior of fenoprofen enantiomers and the fenoprofen-andrographolide interaction.

Immediate release three-layered chewing gum tablets of fenoprofen calcium: preparation, optimization and bioavailability studies in healthy human volunteers.

A three-layered gum tablet (1800 mg), containing 200 mg of Fenoprofen Calcium (Fn) with an inner core containing the drug, and two external layers containing antiadherent lubricant, has been prepared using direct compression. A 2(3) factorial plan has been designed to evaluate the effect of formulation variables namely, Pharmagum(®) M concentration, Maltodextrin type, and Co-adjuvant type on the release characteristics of Fn from the prepared tablets. The formula consisting of 65% Pharmagum(®) M, 75% Maltodextrin DE 39 and 5% Talc comparatively exhibited the highest release (66.59% ± 2.39) in the mouth after 5 min of chewing. Binary and ternary ß-cyclodextrin (ß-CD) complexation was adopted to enhance the release of Fn from the selected gum tablet. The highest significant release (p < 0.05) was achieved from the lyophilized ternary complex containing 100 mg of Fn in presence of polyvinylpyrrolidone (PVP K(25)), exhibiting a release of 88.25% ± 0.93 after 5 min of chewing. The relative bioavailability of the selected gum tablet was found to be 166.06% compared to Nalfon(®) 200 mg capsules. Reduction of the dose to 100 mg exhibited faster absorption rate than Nalfon(®) capsules. The obtained results suggest the possibility of reducing the dose of Fn in chewing gum.

Enantioselective kinetic disposition of fenoprofen in rats with experimental diabetes or adjuvant-induced arthritis.

This study was aimed to investigate the influence of diabetes or arthritis on the enantioselective metabolism and kinetic disposition of fenoprofen in rats with streptozotocin-induced diabetes or Mycobacteriumtuberculosis adjuvant-induced arthritis. Animals received i.v. 10 mg/kg racemic fenoprofen and blood samples were collected up to 24 h thereafter, with 5 animals studied at each time point. Plasma concentrations of the fenoprofen enantiomers were determined by HPLC. Diabetic and arthritic animals showed significant differences when compared with respective controls for the following pharmacokinetic variables of the (+)-(S)-fenoprofen eutomer: area under the plasma concentration time curve, total clearance and volume of distribution. The results indicate that experimental diabetes and adjuvant-induced arthritis influence the fenoprofen enantioselective metabolism.