clinicsofoncology.com 1 Clinics of Oncology Case Report ISSN: 2640-1037 Volume 4 Chronopharmacokinetics Variation of Doxorubicin in a Pediatric Patient with Osteosarcoma Triggers Adverse Effects Gándara-Mireles JA 1,5 , Lares-Asseff I 1,5,* , Carrete Ramírez FA 2 , Reyes Espinoza EA 2 , Patrón Romero L 3 , Reyes Almanza H 3,4,5 Loera Castañeda V 1,5 , Chairez Hernandez I 1 and Villanueva Fierro I 1,5 1 Academia de Genómica / Instituto Politécnico Nacional, CIIDIR-Unidad Durango, México 2 Servicio de Oncohematología pediátrica / Centro Estatal de Cancerología, CECAN Durango, México 3 Facultad de Medicina y Psicología de la Universidad Autónoma de Baja California, México 4 Universidad Tecnológica de Tijuana, México 5 Red Latinoamericana de Implementación y Validación de Guías Clínicas Farmacogenómicas (RELIVAF-CYTED) Keywords: Osteosarcoma; Doxorubicin; shock and chro- nopharmacokinetics Received: 10 Mar 2021 Accepted: 24 Mar 2021 Published:31 Mar 2021 Copyright: ©2021 Ismael LA, et al. This is an open access article dis- tributed under the terms of the Creative Commons Attribu- tion License, which permits unrestricted use, distribution, and build upon your work non-commercially. Citation: Ismael LA, Chronopharmacokinetics Variation of Doxo- rubicin in a Pediatric Patient with Osteosarcoma Triggers Adverse Effects. Clin Onco. 2021; 4(4): 1-5 1. Abstract 1.1. Aims: This is a case report that exemplifies the chronophar- macokinetic differences of Doxorubicin (Dox), depending on time of administration of the drug because of biological rhythms, and its repercussions on adverse reactions. 1.2. Case Report: A 9-year-old female patient with Osteosarcoma (OS), with two pharmacokinetic studies of DOX conducted, in two different days, received two 48 hours-long intravenous infusions of this drug. There was a two-week period in-between, maintain- ing the same length of administration, and only differing by the time of day the first starting at 16 hours and the second at 2 hours am. 1.3. Results: There were no adverse effects in the patient at the end of the first infusion. However, after 8 hours of completing the second infusion with DOX, the patient presented a state of shock, low blood pressure and symptoms including extreme fatigue, dis- orientation, nausea, diarrhea, and general pain. The pharmacoki- netic profiles obtained at the end of each infusion revealed that during the second infusion, the patient had a greater area under the curve (1.626 ng/h /ml vs 1.391 ng /h/ ml), with a much shorter half-life time (2.19 hours vs. 6.63 hours t1/2). 1.4. Conclusions: Our report suggests that these adverse effects may be related to the time of drug was administrated by effects of biological rhythms. 2. Introduction OS is the most common type of primary malignant bone tumor, and is defined by the presence of malignant mesenchymal cells that produce osteoid or immature tissue. The most frequent type of OS is the high-grade central OS, typically presenting in the first or second decade of life, during the period of accelerated growth in adolescence, suggesting that bone growth and pubertal hormones are important in the etiology of the disease [1-2]. Unfortunate- ly, clinical outcomes and therapeutic advances for osteosarcoma treatment have not substantially improved over the last 35 years. This lagging in therapeutic advances may be explained by the ge- netic, epigenetic and biological complexities of this rare tumor. Approved in 1967 in Europe and in 1974 in the United States of America, Doxorubicin (DOX) was introduced as a treatment for various neoplasms, including OS [3-4]. Since then, chemotherapy with DOX has been an essential part of the treatment protocol of OS patients [5-6]. However, it is known that it can also gener- ate various adverse effects and even some types of toxicity [7-8]. The therapeutic window for DOX dosing is narrow, so a better understanding of the pharmacokinetics in children with OS is cru- * Corresponding author: Ismael Lares-Asseff, Academia de Genómica / Instituto Politécnico Nacional, CIIDIR-Unidad Durango, Méxi- co.,Tel and Fax: +52 6188142091; E-mail: ismaelares@yahoo.com