Pharmacokinetic properties of single-dose loratadine and ambroxol alone and combined in tablet formulations in healthy men.
BACKGROUND
Due to Mexico's complicated socioeconomic environment, causing a high occurrence of >1 person sharing a single room, respiratory conditions are spread easily. Respiratory conditions are the main reason for consultation with a physician. The most frequent symptoms are throat soreness and cough; therefore, a new formulation combining loratadine and ambroxol hydrochloride was designed to treat these 2 major symptoms. The combination is expected to provide relief when coprescribed with more specific therapies, such as antibiotics.


OBJECTIVE
This study determined the pharmacokinetic profile of single-dose loratadine-ambroxol hydrochloride combination therapy versus each component given separately. The analyses included descarboethoxyloratadine (DCL), the primary active metabolite of loratadine.


METHODS
This was a 4-week, single-center, randomized, open-label, 3-period crossover study in adult male volunteers aged 18 to 50 years and in good general health. Subjects were randomized to receive single doses of treatment A (2 loratadine 5-mg tablets + ambroxol 30-mg tablets), B (2 ambroxol 30-mg tablets), or C (1 loratadine 10-mg tablet) in 1 of 3 sequences (ABC, BCA, or CAB) per period. A 14-day washout period separated each treatment period. Plasma concentration-time data curves for each subject and treatment were analyzed by noncompart-mental methods to obtain values for area under the curve (AUC), maximum plasma concentration (C(max)), and time to reach C(max) (T(max)).


RESULTS
Thirty subjects (mean [SD] age, 22.5 [2.6] years) were enrolled. All treatments were well tolerated. Formulations A and C produced similar loratadine and DCL AUC from time 0 to 24 hours (AUC(0-24)) values, but showed slightly high C(max). values for loratadine and slightly low C(max) values for DCL, indicating failure to demonstrate bioinequivalence. Formulations A and B produced similar ambroxol C(max), T(max), and AUC(0-24) values.


CONCLUSIONS
In this population of healthy mate volunteers, results showed the bioavailability of loratadine and ambroxol from the new formulation and did not show impairment of absorption when the drugs were formulated in a combination tablet.
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000551:Ambroxol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004338:Drug Combinations; D005100:Expectorants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D017336:Loratadine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000097:blood; D011725:Pyridines / Q000097:blood; D013607:Tablets; D013997:Time Factors
D004338:Drug Combinations; D005100:Expectorants; D006633:Histamine Antagonists; D010880:Piperidines; D011725:Pyridines; D013607:Tablets; D000551:Ambroxol; D017336:Loratadine; C121345:desloratadine