Variable absorption of clavulanic acid after an oral dose of 25 mg/kg of Clavubactin and Synulox in healthy cats

• Published in: TheScientificWorld 2002-05, Vol.2, p.1369-1378
• Main Authors: Vree, Tom B, Dammers, Erik, van Duuren, Eri
• Format: Article
• Language: English
• Subjects: Administration, Oral; Amoxicillin - administration & dosage; Amoxicillin - blood; Amoxicillin - pharmacokinetics; Amoxicillin-Potassium Clavulanate Combination - administration & dosage; Amoxicillin-Potassium Clavulanate Combination - blood; Amoxicillin-Potassium Clavulanate Combination - pharmacology; Animals; Cats; Clavulanic Acid - administration & dosage; Clavulanic Acid - blood; Clavulanic Acid - pharmacokinetics; Cross-Over Studies; Drug Evaluation - veterinary; Drug Therapy, Combination - administration & dosage; Drug Therapy, Combination - blood; Drug Therapy, Combination - pharmacokinetics; Fasting; Female; Tablets - administration & dosage; Tablets - pharmacokinetics
• ISSN: 1537-744X; 2356-6140; 1537-744X
• DOI: 10.1100/tsw.2002.287

The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration-time curves of amoxicillin and clavulanic acid in cats, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration-time curves obtained following a single-dose, open, randomised, two-way crossover phase-I study, each involving 24 female cats treated with two Amoxi-Clav formulations (formulation A was Clavubactin and formulation was B Synulox; 80/20 mg, 24 animals, 48 drug administrations). Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods. The half-life of elimination of amoxicillin is 1.2 h (t1/2 = 1.24 +/- 0.28 h, Cmax = 12.8 +/- 2.12 microg/ml), and that of clavulanic acid 0.6 h (t1/2 = 0.63 +/- 0.16 h, Cmax = 4.60 +/- 1.68 microg/ml). There is a ninefold variation in the AUCt of clavulanic acid for both formulations, while the AUCt of amoxicillin varies by a factor of two. The highest clavulanic acid AUCt values indicate the best absorption; all other data indicate less absorption. Taking into account that the amoxicillin-to-clavulanic acid dose ratio in the two products tested was 4:1, the blood concentration ratios may actually vary much more, apparently without compromising the products" high efficacy against susceptible microorganisms.