Bioavailability of two oral formulations of loratadine 20 mg with concomitant ketoconazole: an open-label, randomized, two-period crossover comparison in healthy Mexican adult volunteers.
BACKGROUND
Loratadine is a long-acting antihistamine with selective peripheral histamine H(1)-receptor antagonistic activity and fewer sedative effects compared with conventional antihistamines, and is widely used in Mexico. Although several generic formulations of loratadine are available in Mexico, based on a literature search, information concerning the bioavailability of each formulation in the Mexican population is not available.


OBJECTIVE
The aim of this study was to compare the bioavailability and tolerability of 2 oral formulations of loratadine 20 mg (two 10-mg tablets) used in Mexico: Sensibit (test formulation; Laboratorios Liomont S.A. de C.V., Mexico City, Mexico) and Clarityne (reference formulation; Schering-Plough S.A. de C.V., Mexico City, Mexico) in healthy volunteers.


METHODS
This open-label, randomized, 2-period crossover study was conducted at Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico. Eligible subjects were healthy male Mexican volunteers aged > or=18 years. Subjects were randomly assigned to receive a single 20-mg dose (two 10-mg tablets) of the test or reference formulation, followed by a 2-week washout period, followed by the same dose of the alternate formulation. A 400-mg dose of ketoconazole (2 doses in 24 hours) was administered to each subject before the administration of each formulation, and a 200-mg dose of ketoconazole was given together with each formulation (ie, a total of 600 mg of ketoconazole was administered). Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including C(maX), AUC(0-t), and AUC(0-infinity), blood samples were drawn at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 5, 8, 12, 16, and 22 hours after dosing. The formulations were considered bioequivalent if the geometric mean ratios of C(maX) and AUC were within the predetermined equivalence range of 80% to 125%. Tolerability was assessed by monitoring vital signs and subject interview regarding the potential presence of adverse events (AEs).


RESULTS
Thirty-two subjects were enrolled in the study (mean age, 22 years [range, 18-28 years]; mean weight, 68.9 kg [range, 58-79 kg]; mean height, 170.8 cm [range, 158-183 cm]). Sixteen subjects received the test formulation first. No period or sequence effect was observed. The 90% CIs for the corresponding ratios of CmaX, AUC(0-t), and AUC(0-infinity) were 81.43% to 106.01%, 83.12% to 100.23%, and 84.06% to 101.10% (all, P < 0.05), meeting the predetermined criteria for bioequivalence. Similar results were found for data without a logarithmic transformation. No AEs were reported throughout the study.


CONCLUSIONS
In this small study in healthy Mexican volunteers, a single, 20-mg dose of the test formulation of loratadine was found to be bioequivalent to that of the reference formulation based on the rate and extent of absorption when concomitantly administered with ketoconazole. Both formulations were well tolerated.
Department of Pharmacology and Toxicology, Universidad Autónoma de Nuevo León, Monterrey, NuevoLeon, Mexico.
Alfredo
A
Piñeyro-López
Everardo
E
Pineyro-Garza
Oscar
O
Torres-Alanís
Raúl
R
Reyes-Araiza
Magdalena
M
Gómez Silva
Noemí
N
Wacksman
Rubén
R
Lujàn Rangel
Alberto
A
de Lago
Daniel
D
Trejo
Mario
M
Gonzàlez-de la Parra
Salvador
S
Namur
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D006967:Hypersensitivity / Q000097:blood* / Q000188:drug therapy; D007654:Ketoconazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017336:Loratadine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D012016:Reference Values
D000935:Antifungal Agents; D039563:Histamine H1 Antagonists, Non-Sedating; D017336:Loratadine; D007654:Ketoconazole