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Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Irinotecan has also demonstrated animal embryotoxicity at doses equivalent to recommended human levels. Teratogenic effects include visceral and skeletal abnormalities, as well as some external defects. Furthermore, rats administered irinotecan after organogenesis and through weaning had decreased learning ability and decreased fetal weights in the female offspring (74). Unlike topotecan, there has been a single report of the use of irinotecan in pregnancy. A 34-year-old patient was diagnosed with recurrent colon cancer, metastatic to a single ovary at 15 weeks of gestation. She underwent surgical resection and, starting at 18 weeks, was treated with 10 courses of 5-FU and irinotecan over the next 5 months. She delivered a healthy infant at 37 weeks, with no appreciated teratogenic or developmental effects at 4 months (75).
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
UGT1A1 testing is used to identify patients who may be at risk of developing severe toxicity to the anticancer agent irinotecan (CamptoTM or CamptosarTM). Irinotecan is a topoisomerase inhibitor commonly prescribed for a number of cancers including colorectal, lung, and pancreatic. UGT1A1 testing is also used to identify individuals at increased risk of adverse drug reactions from other agents metabolized by UGT1A1 such as atazanavir, pazopanib, nilotinib, and belinostat.
An Introduction to the Ethnopharmacology of Wild Plants
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
Shandesh Bhattarai, Christiane Mendes Feitosa, Mahendra Rai
The first agents to advance into clinical use were the isolation of the vinca alkaloids, vinblastine, and vincristine from Catharanthus roseus, for the treatment of cancer followed by the discovery of paclitaxel from Taxus brevifolia (Kinghorn 1994, Kaur et al. 2011). Various parts of the Taxus have been used for the treatment of some noncancerous cases (Crag and Newmann 2005). Taxus baccata was also reported for the treatment of cancer. Paclitaxel is significantly active against ovarian cancer, advanced breast cancer, and lung cancer. Topotecan is used for ovarian and lung cancer from Xi shu tree [Camptotheca acuminata] (Steenhuysen 2007). Camptothecin, isolated from Camptotheca acuminate, is used for the treatment of ovarian and small cell lung cancers, and colorectal cancers (Kinghorn 1994, Creemer et al. 1996, Bertino 1997). Irinotecan is used for colon cancer treatment from Xishu tree [Camptotheca acuminate] (Online Medical Dictionary 2007). Epipodophyllotoxin was isolated as the active antitumor agent from the roots of Podophyllum species, Podophyllum peltatum and Podophyllum emodi, used in the treatment of lymphomas and bronchial and testicular cancers (Harvey 1999). The Podophyllum peltatum and P. emodii are used for the skin cancers.
Understanding the role of chronopharmacology for drug optimization: what do we know?
Published in Expert Review of Clinical Pharmacology, 2023
Akio Fujimura, Kentaro Ushijima
There is a sex-related difference in the safety profile of chronotherapy when using anti-cancer drugs. Neutropenia was found to be significantly more common in women than in men during chronomodulated chemotherapy with 5-FU-leucovorin and oxaliplatin [84]. Moreover, men, but not women, who receive chronomodulated chemotherapy have been found to live significantly longer than those who receive conventional chemotherapy [85]. However, while a chronopharmacological approach seems to have a less favorable outcome in women with metastatic colorectal cancer, there has been a clinical trial that demonstrated a benefit of chronomodulated triplet therapy in female patients [86]. In that study, irinotecan was infused with peak delivery times scheduled at 01:00, 05:00, 09:00, 13:00, 17:00, or 21:00 on day 1, followed by infusion of 5-FU + leucovorin peaking at 04:00 and oxaliplatin peaking at 16:00 for consecutive 4 days. The results showed that the timing of irinotecan infusion influenced the incidence of adverse effects, with a reduction in grade 3–4 toxicities following peak delivery of irinotecan in the afternoon in women and in the morning in men.
Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs
Published in Drug Metabolism Reviews, 2023
Amina Džidić-Krivić, Jasna Kusturica, Emina Karahmet Sher, Nejra Selak, Nejra Osmančević, Esma Karahmet Farhat, Farooq Sher
Irinotecan, also called CPT-11 is an anti-cancer chemotherapeutic drug mostly used intravenously to treat colon cancer. The side effect of irinotecan is severe diarrhea caused by the action of symbiotic enzymes called b-glucuronidases, produced from bacteria in the gut that activates this drug into its active metabolic form. These enzymes are mostly responsible for irinotecan reactivation in the gut and the development of side effects such as severe diarrhea that are mitigated or avoided by the use of their inhibitors. The bacteria involved are Clostridium ramosum, Escherichia coli and Bacteroides vulgatus. Wallace et al. (2010) found that oral intake of inhibitor of bacterial enzymes such as microbial b-glucuronidases, protected mice from CPT-11-induced toxicity.
Effects of common genetic variants of human uridine diphosphate glucuronosyltransferase subfamilies on irinotecan glucuronidation
Published in Toxicology Mechanisms and Methods, 2023
Kouji Tagawa, Yoshihiro Maruo, Yu Mimura, Shinichi Ikushiro
Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin) is a semisynthetic analog of the cytotoxic alkaloid camptothecin. Irinotecan is widely used for the treatment of colorectal, pancreatic, and lung cancers because of its anticancer activity (de Man et al. 2018). It is converted to the active metabolite 7-ethyl-10 hydroxycamptothecin (SN-38) by carboxylesterase (de Man et al. 2018). SN-38 is further glucuronidated to the inactive metabolite SN-38 glucuronide (SN-38G) by uridine diphosphate glucuronosyltransferase 1A (UGT1A) subfamily members (Haaz et al. 1997; Hanioka et al. 2001). In this catalytic reaction, uridine-5′-diphosphoglucuronic acid (UDPGA) acts as a co-substrate for the formation of hydrophilic glucuronides from non-membrane-associated substrates, such as steroids, bile acids, bilirubin, hormones, dietary constituents, and various drugs, environmental xenobiotics, and carcinogens (Tukey and Strassburg 2000). Tissue-specific expression varies among UGT1A subfamily members (Tukey and Strassburg 2000). UGT1A1, UGT1A3, UGT1A4, UGT1A6, and UGT1A9 are expressed in the human liver, whereas UGT1A5 is expressed in the human thymus, UGT1A7 in the human tonsil and kidney, UGT1A8 in the human bladder, and UGT1A10 is expressed in the human intestine (Izukawa et al. 2009; Basit et al. 2020; Zhang H et al. 2020). Moreover, substances that can be glucuronidated are different for each UGT1A subfamily member (Maruo et al. 2010). UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 can glucuronidate SN-38 (Hanioka et al. 2001; Gagné 2002).