Effects of P-glycoprotein inductor rifampicin on pharmocokinetics of tulathromycin in goats

Tulathromycin is an effective macrolide antibiotic frequently used in respiratory system infections. Objective of this study was determination pharmacokinetic profile of tulathromycin relation with rifampicin which is a P-gp transporter protein inducer. Activated P-gp may change dose, delivery and interval time of many drugs. Healthy male hybrid (F1) Alpine-Hair goats were allocated into three groups (n=8) as Group A, B and C. Group A goats received only single 2.5 mg/kg dose subcutaneous tulathromycin. Group B goats received at first 7 days of the experiment oral 10 mg/kg/day rifampicin and 8th day single dose subcutaneous 2.5 mg/kg tulathromycin. Group C goats received at first 7 days of the experiment oral 10 mg/kg/day rifampicin and 8th day single dose subcutaneous 2.5 mg/kg tulathromycin followed by 8-15th days oral 10 mg/kg/day rifampicin. Blood samples were taken from Vena jugularis, before and after the drug administration (0.016 to 360. h) at heparinized tubes. Plasma samples were analysed by liquid chromatography mass spectrometry (LC-MS/MS). Detected Group A peak plasma concentration (Cmax) of tulathromycin was 1390,97±173,65, and Group B and C (rifampicin+tulathromycin) values were 958,21±106,31 and 807,21±116,82 ng/ml, respectively. When compared Cmax values among all groups, Group A value was significantly higher than the groups B and C (P<0.05). Group A, B and C detected mean residence time based on time zero to last sample time (MRTlast) values were 52.16±1.87, 56.04±4.70 and 66.75±4.30 hour, respectively and, determined mean residence time based on time zero extrapolated to infinity (MRTINF_obs) values were 69.28±4.64, 85.90±5.75, 86.76±4.69 hour, respectively. When compared of MRTlast and MRTINF_obs values among the groups, rifampicin administered groups (group B and C) values were higher than the group A. These differences among the groups found significant (P<0.05). Study findings suggest that the rifampicin use in goats may change several pharmacokinetic parameters of tulathromycin. Although, in order to comprehend the effects of rifampicin on tulathromycin pharmacokinetic parameters requires further in vitro studies on CYP enzymes and the P-gp transport systems.