Comparative pharmacokinetics of a new oral long-acting formulation of doxycycline hyclate: A canine clinical trial

• Published in: European journal of pharmaceutical sciences 2015-12, Vol.80, p.9-15
• Main Authors: Arciniegas Ruiz, Sara Melisa, Gutiérrez Olvera, Lilia, Bernad Bernad, María Josefa, Caballero Chacón, Sara del Carmen, Vargas Estrada, Dinorah
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Antibiotics; Canine; Carbopol; Cross-Over Studies; Delayed-Action Preparations; Dogs; Doxycycline - blood; Doxycycline - pharmacokinetics; Eudragit; Female; Long-acting; Male; Tetracyclines
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2015.09.012

Doxycicline is used in dogs as treatment of several bacterial infections, mycoplasma, chlamydia and rickettsial diseases. However, it requires long treatments and several doses to be effective. The aim of this study was to determine the pharmacokinetics of four formulations of doxycycline hyclate, administered orally, with different proportions of excipients, acrylic acid–polymethacrylate-based matrices, to obtain longer therapeutic levels than conventional formulation. Forty-eight dogs were randomly assigned in five groups to receive a single oral dose (20mg/kg) of doxycycline hyclate without excipients (control) or a long-acting formulation containing doxycycline, acrylic acid polymer, and polymethacrylate in one of the following four proportions: DOX1(1:0.25:0.0035), DOX2(1:0.5:0.0075), DOX3 (1:1:0.015), or DOX4(1:2:0.0225). Temporal profiles of serum concentrations were obtained at several intervals after each treatment. Therapeutic concentrations were observed for 60h for DOX1 and DOX4, 48h for DOX2 and DOX3 and only 24h for DOX-C. None of the pharmacokinetic parameter differed significantly between DOX1 and DOX2 or between DOX3 and DOX4; however, the findings for the control treatment were significantly different compared to all four long-acting formulations. Results indicated that DOX1 had the most adequate pharmacokinetic–pharmacodynamic relationships for a time-dependent drug and had longer release times than did doxycycline alone. However, all four formulations can be effective depend on the minimum effective serum doxycycline concentration of the microorganism being treated. These results suggest that the use of any of these formulations can reduce the frequency of administration, the patient's stress, occurrence of adverse effects and the cost of treatment. [Display omitted]