Pharmacokinetic variability of anticancer agents

Undevia, Samir D.; Gomez-Abuin, Gonzalo; Ratain, Mark J.

doi:10.1038/nrc1629

Cited by 221 publications

(164 citation statements)

References 125 publications

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“…Circulating concentrations of phytochemicals, such as psoralens, lignans, and the flavonoids naringenin and hesperitin, can vary widely among individuals even in the context of controlled feeding studies [8][9][10]. The process of phytochemical disposition, like that of disposition of drugs and other xenobiotics, involves absorption, metabolism, distribution, and excretion, and each of these parts may contribute to pharmacokinetic variability (Figure 1) [11].…”

Section: Sources Of Variation In Phytochemical Metabolism and Disposimentioning

confidence: 99%

Interindividual differences in phytochemical metabolism and disposition

Lampe

Chang

2007

Seminars in Cancer Biology

110

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Many phytochemicals, the bioactive nonnutrient compounds found in plant foods, possess biologic effects associated with reduced risk of various diseases such as cancer. Genetic variation in pathways affecting absorption, metabolism, and distribution of phytochemicals is likely to influence exposure at the tissue level, thus modifying disease risk in individuals. Few studies have examined these genephytochemical interactions in humans. In this review, we discuss the sources of variation in metabolism and disposition of phytochemicals, and focus on two aspects of phytochemical handling that have received some attention: the impact of intestinal bacteria and genetically polymorphic phase II, conjugating enzymes.

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Section: Sources Of Variation In Phytochemical Metabolism and Disposimentioning

confidence: 99%

Interindividual differences in phytochemical metabolism and disposition

Lampe

Chang

2007

Seminars in Cancer Biology

110

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“…Interindividual pharmacokinetic and pharmacodynamic variability is usually substantial and may be augmented by pregnancy (1). During pregnancy multiple changes in physiology occur affecting the major pharmacokinetic processes including absorption, distribution, metabolism and excretion (2).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study

Calsteren¹,

Verbesselt

Ottevanger

et al. 2010

Acta Obstet Gynecol Scand

104

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Objective. To determine the impact of physiologic changes of pregnancy on pharmacokinetics of chemotherapeutic agents. Design. A preclinical and a clinical case-control trial. Setting. Institute of Primate Research Nairobi and collaborating hospitals in Belgium, the Netherlands and Czech Republic. Population. Pregnant and nonpregnant women and baboons receiving chemotherapy. Methods. Chemotherapy pharmacokinetics was compared between the pregnant and nonpregnant state. Standard-dosed chemotherapy regimens were administered in pregnant and nonpregnant baboons/women, followed by serial blood samplings. Drug plasma levels were determined using high performance liquid chromatography and atomic absorption spectrometry. Main outcome measures. Area under the curve (AUC), maximal plasma concentration, terminal elimination half-life, clearance and distribution volume of each drug in pregnant and nonpregnant state. Results. Intraindividual comparative pharmacokinetic data were obtained for doxorubicin and paclitaxel/platinum in three and two baboons, respectively. In the clinical trial, two patients were exposed to doxorubicin and one patient was exposed to paclitaxel/ platinum during and after pregnancy. Furthermore, a pooled analysis was performed based on 16 cycles of pregnant and 11 cycles of nonpregnant women. Numbers of pregnant/nonpregnant patients were 5/2, 7/5, 4/4 and 2/2 for paclitaxel, doxorubicin, epirubicin and platinum, respectively. For all drugs tested in the preclinical and clinical study, a decreased AUC and maximal plasma concentration and an increased distribution volume and clearance were observed in pregnancy. Conclusions. Although numbers were too small for statistical significance, pregnancy-associated physiologic alterations appear to lead to a decrease in plasma exposure of chemotherapeutic drugs. The importance of long-term follow-up of women treated with chemotherapy during pregnancy is underscored.

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“…chemotherapy or cardiovascular diseases [1], [2]. However, a CYP isoform can detect several different compounds at the same time due to the broad substrate range of cytochrome and to its molecular structure [6], not allowing a correct identification and quantification of the drug compound.…”

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confidence: 99%

A Linear Approach to Multi-Panel Sensing in Personalized Therapy for Cancer Treatment

2013

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Abstract-In this paper, a new approach for evaluating the performance of a multi-panel biosensor using linear algebra is presented. With a system-level mathematical analysis based on graphs and linear algebra, we formulate a new approach for contributions decoupling in a multi-panel biochip for simultaneous detection of anti-cancer drugs, avoiding redundancy and interaction between enzymes. Experimental results have been used to validate the model. Index Terms-Cytochrome P450 biosensor, multiplexed drugs detection, personalized therapy, condition number, limit of detection, linear system.

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Pharmacokinetic variability of anticancer agents

Cited by 221 publications

References 125 publications

Interindividual differences in phytochemical metabolism and disposition

Interindividual differences in phytochemical metabolism and disposition

Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study

A Linear Approach to Multi-Panel Sensing in Personalized Therapy for Cancer Treatment

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