Bioavailability of two oral formulations of a single dose of levofloxacin 500 mg: an open-label, randomized, two-period crossover comparison in healthy Mexican volunteers.
BACKGROUND
Levofloxacin is a synthetic fluoroquinolone with a broad spectrum of antibacterial activity. It is indicated for the treatment of respiratory, sinus, skin, and urinary tract infections. Although generic formulations of oral levofloxacin are marketed in Mexico, a literature search did not identify published data concerning the bioavailability of these formulations; these data would be relevant to secure marketing of a test formulation in Mexico.


OBJECTIVE
The aim of this study was to compare the bioavailability and determine the bioequivalence of a test formulation (an oral tablet containing levofloxacin 500 mg) with its corresponding listed reference-drug formulation in Mexico (a list issued by Mexican Health Authorities).


METHODS
A single-dose, open-label, randomized-sequence, 2-period crossover design was used in this study. Eligible participants were healthy Mexican adults of either sex, randomly assigned to receive the test formulation followed by the corresponding reference formulation, or vice versa, with a 1-week washout period between doses. After a 10-hour overnight fast, the participants received the assigned formulation. Plasma concentrations of levofloxacin were determined using high-performance thin-layer chromatography, and densitometric analysis was performed at 300 nm. For the analysis of pharmacokinetic parameters, including C(max), AUC0(-24), and AUC(0-infinity)), blood samples were drawn at baseline and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after administration. The test formulation was considered to meet the criteria for bioequivalence if the geometric mean ratios (test/reference) were with- in the predetermined range of 80% to 125%. Tolerability was determined by clinical assessment, vital signs, laboratory analysis, and interviews with participants about adverse events.


RESULTS
A total of 26 participants were enrolled, including 14 men and 12 women with a mean (SD) age of 24 (4) years (range, 18-34 years), weight of 62.2 (10.0) kg (range, 45.5-80.0 kg), height of 163 (9) cm (range, 148-176 cm), and body mass index of 23.3 (2.4) kg/m(2) (range, 19.2-27.1 kg/m(2)). The 90% CIs for log-transformed C(max), AUC(0-24), and AUC(0-infinity) were 94.48% to 106.22%, 90.01% to 116.44%, and 85.11% to 114.00%, respectively. Eleven participants reported a total of 20 adverse events during the study. None of the adverse events were considered serious.


CONCLUSIONS
In this small study in healthy, fasting Mexican adults, a single 500-mg dose of the test formulation of orally administered levofloxacin met the regulatory requirements to assume bioequivalence based on the rate and extent of absorption. Both formulations were well tolerated.
Galan-Herrera
Juan Francisco
JF
Pharmacology Research Unit, Medica Sur Hospital and Clinical Foundation, Mexico City, Mexico.
Poo
Jorge Luis
JL
Rosales-Sanchez
Oscar
O
Fuentes-Fuentes
Elvira
E
Cariño
Lizbeth
L
Burke-Fraga
Victoria
V
Namur
Salvador
S
Parra
Mario González-de la
MG
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002855:Chromatography, Thin Layer / Q000379:methods; D018592:Cross-Over Studies; D003720:Densitometry; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008800:Mexico; D015242:Ofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency; D013997:Time Factors; D055815:Young Adult
D000900:Anti-Bacterial Agents; D013607:Tablets; D064704:Levofloxacin; D015242:Ofloxacin