The aim of this study was to develop an oral drug formulation of doxycycline hyclate that maintain longer therapeutic levels than conventional forms. A polymethacrylate and acrylic acid based matrix were used in different proportions to obtain controlled-release formulations; DOX1, DOX2 and DOX-C (without excipients). Serum concentrations vs. time profile were investigated after their oral administration in healthy dogs. DOX1 and DOX2 showed therapeutic concentrations for 60 hours, while DOX-C only 24 hours. The pharmacokinetic values obtained were K½el, Cmax, Tmax, AUC, AUC∞, AUCt, AUMC, RT, Kel, Vdss, Clb and Frel. DOX1 did not differ significantly from DOX-C but showed significant differences in all variables with DOX2 (p<0.05). In conclusion DOX1 had the best pharmacokinetics-pharmacodynamics relationship for time-dependent drug and longer release time (60 hours), thereby reducing the frequency of administration, the patient's stress, the occurrence of adverse effects and the cost of treatment.