Bioavailability of two oral suspension and two oral tablet formulations of nimesulide 100 mg in healthy Brazilian adult subjects.
A specific, fast and sensitive high performance liquid chromatography coupled to an electro spray tandem triple quadrupole mass spectrometer (LC-MS/MS) assay was developed for the determination of nimesulide in human plasma using carbamazepine as the internal standard. The lower limit of quantification (LLOQ) was 50 ng/ml and the calibration curves were linear in the concentration range of 50 - 6,000 ng/ml. Method inter-batch precision and accuracy ranged from 2.78 to 10.80%, and 94.92 to 102.46%, respectively. Intra-batch precision ranged from 2.44 to 7.74%, while intra-batch accuracy ranged from 91.70 to 104.73%. The analytical method was applied to evaluate the pharmacokinetic and relative bioavailability of two different pharmaceutical formulations containing nimesulide, one tablet and one oral suspension, manufactured by the same pharmaceutical factory, comparing with two reference Nisulid formulations in 52 volunteers of both sexes previously divided in two groups of 26 subjects (13 men and 13 females each group). The test tablet formulation was not bioequivalent to the Nisulid 100 mg tablet with respect to the rate of absorption, but was bioequivalent according to the extent of drug absorption. On the other hand, since the 90% CI for Cmax, AUC0-t and AUCinf were within the 80 - 125% interval in the oral suspension study, it was concluded that test oral suspension were bioequivalent to Nisulid 50 mg/ml with respect to both the rate and extent of absorption.
Rigato
H M
HM
Department of Medical Clinic, State University of Campinas, Campinas, SP, Brazil.
Borges
B C
BC
Sverdloff
C E
CE
Moreno
R A
RA
Orpineli
E
E
Carter Borges
N
N
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001938:Brazil; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013535:Suspensions; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013449:Sulfonamides; D013535:Suspensions; D013607:Tablets; C012655:nimesulide