Pharmacokinetics of matrine and amoxicillin in pigs after gavage administration of each drug alone and in combination

Abstract

Background Matrine (MT) exhibits antibiotic resistance reversal and antiviral activities in vitro. However, the in vivo efficacies of MT and amoxicillin (AMO)-MT combination cannot be accurately evaluated due to the lack of pharmacokinetics (PK) data. The aim of this study was to investigate the PKs of MT and AMO in pigs after gavage administration of each drug alone and in combination.Results Twenty-four pigs were randomly distributed to three treatments, namely group A (MT, 50 mg/kg), group B (AMO, 50 mg/kg), and group C (MT, 50 mg/kg + AMO, 50 mg/kg). The maximum concentration (C_max), area under the curve from time 0 to 36 h (AUC_{0 → 36 h}), apparent volume of distribution (V_d) and total body clearance (Cl_B) for group A were 1389.73 ± 320.05 µg/L, 4138.16 ± 1245.23 h*µg/L, 63.08 ± 22.24 L/kg and 12.98 ± 3.71 L/h/kg, respectively, versus 21153.92 ± 16967.88 µg/L (P < 0.01), 40239.83 ± 22044.18 h*µg/L (P < 0.01), 9.93 ± 3.86 L/kg (P < 0.01), and 1.61 ± 0.81 L/h/kg (P < 0.01) for group B. Significantly greater T_max, Cl_B, V_d (P < 0.05) and lower C_max, AUC_{0 → 36 h} (P < 0.05) were observed in group A compared to those in group C.Conclusions Compared with AMO, MT was poorly absorbed, extensively distributed and rapid eliminated in pigs. The PK profiles of MT and AMO changed significantly after the combined administration of these two drugs, indicating the occurrence of PK drug-drug interaction between MT and AMO.