An eutomer/distomer ratio near unity does not justify non-enantiospecific assay methods in bioequivalence studies.
The aim of the present investigation was to compare the pharmacokinetics of two tablet formulations of 600 mg of racemic ibuprofen obtained using enantiospecific and non-enantiospecific assays, in order to explore if chiral assays should be employed in bioequivalence studies of chiral active substances. The stereoselective assay showed that, for both formulations, there was an initial phase where (R)-ibuprofen was the predominant enantiomer followed by a final phase where (S)-ibuprofen was the predominant one. Results from both analytical methods proved that the two formulations were bioequivalent. However, the chiral bioanalytical method detected a larger difference in the eutomer than that showed by the nonchiral bioanalytical method. In conclusion, although the exposure ratios of enantiomers are near unity, the measurement of unresolved ibuprofen alone is not an adequate measure of bioequivalence since it may mask the actual difference in the eutomer exposure among formulations.
García-Arieta
Alfredo
A
Division of Pharmacology and Clinical Evaluation, General Subdirection for Human Use Medicines, Spanish Agency for Medicines and Health Care Products, Madrid, Spain.
Abad-Santos
Francisco
F
Rodríguez-Martínez
M Angeles
MA
Varas-Polo
Yolanda
Y
Novalbos
Jesús
J
Laparidis
Nikos
N
Gallego-Sandín
Sonia
S
Orfanidis
Kyriakos
K
Torrado
Juan
J
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D013237:Stereoisomerism; D013607:Tablets; D013810:Therapeutic Equivalency
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013607:Tablets; D007052:Ibuprofen