The bioavailability of diclofenac from enteric coated products in healthy volunteers with normal and artificially decreased gastric acidity.
The relative bioavailability of four monolithic enteric coated (MEC) diclofenac products was compared in 16 healthy volunteers. Only one generic product was fully bioequivalent with the reference product Voltaren with regard to AUC, Cmax, and tlag. Two products showed significant differences in tlag. In a second experiment with eight volunteers the influence of increased gastric pH (ranitidine treatment) on the two mutually most differing products was studied. They showed equivalence in AUC, but not in Cmax. Analysis of tlag suggests that the product with the low tlag disintegrates within the non-acid stomach, whereas the product with the long tlag passes the non-acid stomach intact. Several in vitro dissolution tests were conducted. The European Pharmacopeia test did not detect any differences between the products. At pH 5, both with and without mechanical stress, only the product with the shortest tlag released diclofenac. The in vivo results were best predicted by the in vitro dissolution tests performed at several fixed pH values with mechanical stress.
Van Gelderen
M E
ME
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Olling
M
M
Barends
D M
DM
Meulenbelt
J
J
Salomons
P
P
Rauws
A G
AG
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D004008:Diclofenac / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005744:Gastric Acid / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D011786:Quality Control; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013608:Tablets, Enteric-Coated
D013608:Tablets, Enteric-Coated; D004008:Diclofenac