Effect of ivermectin on the disposition of amoxicillin in rat blood and brain using microdialysis sampling Original Research Article

To gain more insight into the pharmacological role of endogenous p-glycoprotein in the metabolism of the widely used substrate drug amoxicillin, we compared single-dose (20 mg kg−1, i.v.) pharmacokinetics of amoxicillin both with and without coadministration of ivermectin (5 mg kg−1, i.v.) in Sprague–Dawley rats. A rapid and sensitive microbore liquid chromatographic technique for the simultaneous determination of unbound amoxicillin in rat blood and brain has been developed and applied for sampling drugs. Microdialysis probes were inserted into the jugular vein/right atrium and brain striatum of male Sprague–Dawley rats. Amoxicillin (20 mg kg−1, i.v.) was then administered via the femoral vein, and dialysates were sampled from the blood and brain via the microdialysis system. Based on the pharmacokinetic constants, the area under the concentration curve (AUC) ratio of amoxicillin in rat brain and blood was about 4.8%. The observed results suggest that amoxicillin may permeate the blood–brain barrier. In comparison to blood pharmacokinetic data, the mean residence time and the AUC of amoxicillin in ivermectin treated rats were 2.5- and 2.0-fold higher than the control group, respectively. The estimates of brain pharmacokinetic data based on unbound concentrations did not differ between groups. These experiments demonstrate that ivermectin significantly alters the pharmacokinetics of amoxicillin in rat blood but not in rat brain. Possible mechanisms for this interaction include the blocking by ivermectin of the protein binding of amoxicillin with p-glycoprotein in rat plasma.