Relative bioavailability of two oral formulations of piroxicam 20 mg: a single-dose, randomized-sequence, open-label, two-period crossover comparison in healthy Mexican adult volunteers.
BACKGROUND
Piroxicam is an NSAID indicated for the treatment of rheumatoid diseases. Although there are generic formulations of oral piroxicam marketed in Mexico, a literature search did not identify published data concerning the bioavailability of these formulations in the Mexican population.


OBJECTIVE
The aims of this study were to determine the bioequivalence of a generic (test) and a reference formulation of oral piroxicam 20 mg and to generate data regarding the oral bioavailability of this drug in a Mexican population.


METHODS
This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Mexican adult volunteers. Subjects were randomly assigned to receive the test formulation followed by the reference formulation, or vice versa, with a 15-day washout period between doses. Study drugs were administered after a 10-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after administration. Plasma concentrations of piroxicam were determined using HPLC. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%. Tolerability was determined using clinical assessment, monitoring of vital signs, laboratory analysis, and subject interviews regarding adverse events (AEs).


RESULTS
A total of 28 subjects were enrolled (15 men, 13 women; mean [SD] age, 24 [4] years [range, 19-35 years]; weight, 63.0 [8.9] kg [range, 47.5-81.9 kg]; height, 165 [10] cm [range, 149-179 cm]; and body mass index, 23.2 [1.4] kg/m(2) [range, 20.6-26.0 kg/m(2)]). The 90% CIs for piroxicam C(max), AUC(0-infinity), and AUC(0-infinity)) were 89.98% to 101.04%, 91.46% to 101.19%, and 93.51% to 105.86%, respectively. Thirteen subjects reported a total of 17 AEs during the study. None of the AEs were considered serious or related to the administered formulations. The most common AE was local postvenipuncture ecchymosis, reported in 8 subjects (28.6%).


CONCLUSIONS
In this small study in healthy Mexican adult subjects, a single 20-mg dose of the test formulation of orally administered piroxicam met the regulatory requirements to assume bioequivalence, based on the rate and extent of absorption. Both formulations were well tolerated. Mexican national registry code: CE-PEC.0875.
Palma-Aguirre
Jose Antonio
JA
Centro de Estudios Científicos y Clínicos Pharma, S.A. de C.V., Mexico City, Mexico.
Lopez-Gamboa
Mireya
M
Cariño
Lizbeth
L
Burke-Fraga
Victoria
V
González-de la Parra
Mario
M
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D010894:Piroxicam / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D016568:Drugs, Generic; D010894:Piroxicam