5-Fluorouracil (5-FU) is a common anticancer agent used in the treatment of solid tumours, with a reported variability in the pharmacokinetic profile and inter-patient differences in efficacy and toxicity. Since 5-FU is intracellularly metabolised to active cytotoxic fluoronucleotides, some authors suggested it would be useful to determine the plasma levels of its main metabolites 5-fluoro-5,6-dihydrouracil (5-FUH2), 5-fluorouridine (5-FUrd) and 5-fluoro-2'-deoxyuridine (5-FdUrd), in order to better characterise population pharmacokinetics-pharmacodynamics (PK-PD) of this drug. We developed and validated an HPLC method to simultaneously determine plasma concentrations of 5-FU and the three main metabolites, and we analysed the plasma concentration-time curves of the first dose of 18 colon cancer patients treated with folinic acid and 5-FU 400 mg m(-2) by intra-venous bolus injection as adjuvant chemotherapy. Non-compartmental PK analysis has been applied to 5-FU and 5-FUH2 concentrations, estimating the following parameters (median values): Cmax 55.44 and 6.23 microg ml(-1), respectively, AUC(0-2 h) 11.59 and 5.94 hx microg ml(-1), CLTB 30.64 and 51.81 lh(-1) m(-2), 5-FUH2/5-FU AUC ratio 0.47 (range 0.29-1.12). We verified the patient covariables which could influence the inter-patient variability in the area under the time-concentration curves, and we observed that age, sex, weight, body surface area, cycle of therapy, toxicity development and 5-FUrd or 5-FdUrd detectability did not have statistical influence on 5-FUH2/5-FU AUC ratio. In eight subjects, we compared the PK data of the first and the fifth day of dose administration, and we found stable 5-FU values, but the 5-FUH2 disposition decreased with lower AUC(0-2 h) (7.90 hx microg ml(-1) versus 5.99 hx microg ml(-1)) and, particularly, Cmax (8.38 microg ml(-1) versus 5.50 microg ml(-1)) at day 5. This fact, evident in almost every patient, could suggest a possible reduction in the catabolic pathway of 5-FU leading to 5-FUH2, with a possible increase of the therapeutic pathway. For this reason, we tried to detect 5-FUrd and 5-FdUrd and, in fact, in our patients these metabolites were detected only in few samples, but most of them at day 5. In conclusion, our study confirms the relevance of pharmacokinetic analysis of 5-FU main metabolites and especially 5-FUH2, to better understand the metabolism and to improve the therapeutic efficacy.
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http://dx.doi.org/10.1016/j.phrs.2004.01.006 | DOI Listing |
Physiol Res
November 2021
AgroBioTech Research Centre, Slovak University of Agriculture in Nitra, Nitra, Slovak Republic. Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Nitra, Slovak Republic.
Beneficial effects of Sambucus nigra L. (black elder) as a traditional medicine have been associated with the phytoconstituents including polyphenols, terpenes and lectins. Various antioxidant rich natural products have also been implicated with improvement of reproductive health and fertility, however, the effect of Sambucus nigra on the ovarian cell functions has not been investigated yet.
View Article and Find Full Text PDFPhysiol Res
November 2021
Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Nitra, Slovak Republic.
This study aimed to examine the effect of dietary flavonoid isoquercitrin on ovarian granulosa cells using the immortalized human cell line HGL5. Cell viability, survival, apoptosis, release of steroid hormones 17beta-estradiol and progesterone, and human transforming growth factor-beta2 (TGF-beta2) and TGF-beta2 receptor as well as intracellular reactive oxygen species (ROS) generation were investigated after isoquercitrin treatment at the concentration range of 5-100 microg.ml-1.
View Article and Find Full Text PDFAntibiotics (Basel)
March 2021
School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
Marine natural products (MNPs) have been an important and rich source for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein, we report bioassay guided fractionation of marine extracts from sponges , and that led us to identify novel compounds with antimicrobial properties. Tertiary amines or quaternary amine salts: aniline , benzylamine , tertiary amine and , and quaternary amine salt , along with three known compounds () were isolated from a crude extract and MeOH eluent marine extracts.
View Article and Find Full Text PDFPhysiol Res
December 2020
Department of Ecology and Diseases of Zoo Animals, Game, Fish and Bees, University of Veterinary and Pharmaceutical Sciences Brno,Czech Republic.
Diclofenac is a drug commonly used in human and veterinary medicine for the treatment of diseases associated with inflammation and pain. Medicinal products enter waste and surface waters on an everyday basis and contaminate the aquatic environment. Fish are therefore permanently exposed to these chemicals dissolved in their aquatic environment.
View Article and Find Full Text PDFPhysiol Res
December 2017
Department of Life Science and Bioinformatics, Assam University, Silchar, India, Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Nitra, Slovak Republic.
This study aimed at examining the secretion activity of steroid hormones progesterone and 17beta-estradiol by porcine ovarian granulosa cells after addition of green tea extract. Granulosa cells were incubated with green tea extract (at doses of 0.01, 0.
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