Pharmacokinetic Comparison Between Systemic and Local Chemotherapy by Carboplatin in Dogs
Department of Obstetrics and Gynecology, Nanfang Hospital, Guangdong Province, PR China.Reproductive sciences (Thousand Oaks, Calif.) (Impact Factor: 2.23). 08/2009; 16(11):1097-102. DOI: 10.1177/1933719109341999
The aim of the current study was to compare pharmacokinetics of local chemotherapy by pelvic intra-arterial administration with intravenous injection in dogs. A total of 18 female dogs (weight: 10-15 kg) were randomly divided into 3 groups: the peripheral vein administration (group A, n = 6), the abdominal aorta administration (group B, n = 6), and the internal iliac artery administration (group C, n = 6). Carboplatin at a dose of 1.2 mg/kg was administered by infusing into the arteries or the vein. For analysis, plasma and uterine tissue samples were collected at different times following infusion. The peak local concentration of platinum in the uterus of dogs in group C was significantly higher than those of groups A and B (P < .05). The area under the tissue concentration-time curve (AUC) of uterine tissues was significantly higher in dogs of group C compared to those of the other 2 groups (P < .05). There was no significant difference in the AUC of the uterine tissues of dogs between groups A and B (P > .05). The peak concentration of platinum in plasma was significantly higher in group A compared to those of the other 2 administration routes (P < .05). We observed the pharmacokinetic advantages of local chemotherapy by internal iliac artery perfusion with the chemotherapeutic agent, carboplatin, to the uterus, thereby leading to a high-drug concentration that may be more effective in treating cervical cancer.
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ABSTRACT: ABCG2 (ATP binding cassette subfamily G, member 2) mediates resistance to a variety of cytotoxic agents. Although human ABCG2 is well characterized, the function of canine ABCG2 has not been studied previously. Feline ABCG2 has an amino acid substitution in the adenosine triphosphate-binding domain that decreases its transport capacity relative to human ABCG2. Our goal was to compare canine ABCG2-mediated chemotherapeutic drug resistance to feline ABCG2-mediated chemotherapeutic drug resistance. HEK-293 cells stably transfected with plasmid containing canine ABCG2, feline ABCG2 or no ABCG2 were exposed to carboplatin, doxorubicin, mitoxantrone, toceranib or vincristine, and cell survival was subsequently determined. Canine ABCG2 conferred a greater degree of chemotherapy resistance than feline ABCG2 for mitoxantrone. Neither canine nor feline ABCG2 conferred resistance to doxorubicin, vincristine or toceranib. Canine, but not feline, ABCG2 conferred resistance to carboplatin, a drug that is not reported to be a substrate for ABCG2 in other species.
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