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prospective study aimed to evaluate the effect of metronomic cyclophosphamide on carboplatin\u2019s tolerability, efficacy, and pharmacokinetics in dogs with mammary carcinoma. Sixteen female dogs with mammary carcinoma were divided into groups: 300 mg\/m2 intravenous (i.v.) carboplatin therapy (G1 = 8) or 300 mg\/m2 i.v. carboplatin which was associated with 12.5 mg\/m2 oral cyclophosphamide in a metronomic regimen (G2 = 8). The investigated animals underwent a clinical evaluation, a mastectomy, a carboplatin chemotherapy, and serial blood sampling for the pharmacokinetic analysis. The adverse events and survival rates were monitored. A non-compartmental analysis was applied to calculate the pharmacokinetic parameters of carboplatin in the 2nd and 4th chemotherapy cycles. Carboplatin PK showed high interindividual variability with a 10-fold variation in the area under the plasma concentration\u2013time curve (AUC) in G1. The systemic plasma exposure to carboplatin was equivalent in both of the treatments considering the AUC and maximum plasma concentration (Cmax) values. Although the red blood cells (p &lt; 0.0001), platelets (p = 0.0005), total leukocytes (p = 0.0002), and segmented neutrophils (p = 0.0007) were reduced in G2, the survival rate increased (p = 0.0044) when it was compared to G1. In conclusion, adding low daily doses of cyclophosphamide to a carboplatin therapy showed promising outcomes in female dogs with mammary tumors.<\/jats:p>","DOI":"10.3390\/ani12223109","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T19:18:29Z","timestamp":1668107909000},"page":"3109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Pharmacokinetics of Carboplatin in Combination with Low-Dose Cyclophosphamide in Female Dogs with Mammary Carcinoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Mar\u00edlia Carneiro","family":"Machado","sequence":"first","affiliation":[{"name":"Department of Veterinary Anatomy, Pathology and Clinics, School of Veterinary Medicine and Zootechny, UFBA, Salvador 40170-110, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-7960","authenticated-orcid":false,"given":"Priscila Akemi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA"},{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-0389","authenticated-orcid":false,"given":"Leandro Francisco","family":"Pippa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-058X","authenticated-orcid":false,"given":"Nat\u00e1lia Valadares","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiane Maria Fernandes","family":"Neves","sequence":"additional","affiliation":[{"name":"Pharmacokinetics Laboratory, School of Pharmacy, Federal University of Bahia, Salvador 40170-115, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9095-776X","authenticated-orcid":false,"given":"Ricardo Dias","family":"Portela","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Molecular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-7366","authenticated-orcid":false,"given":"Stella Maria","family":"Barrouin-Melo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy, Pathology and Clinics, School of Veterinary Medicine and Zootechny, UFBA, Salvador 40170-110, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1343-3473","authenticated-orcid":false,"given":"Anna","family":"Hielm-Bj\u00f6rkman","sequence":"additional","affiliation":[{"name":"Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Leonor Pardo Campos","family":"Godoy","sequence":"additional","affiliation":[{"name":"Pharmacokinetics Laboratory, School of Pharmacy, Federal University of Bahia, Salvador 40170-115, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9879-7999","authenticated-orcid":false,"given":"Alessandra","family":"Estrela-Lima","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy, Pathology and Clinics, School of Veterinary Medicine and Zootechny, UFBA, Salvador 40170-110, BA, Brazil"},{"name":"Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. 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