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Troisdorf, Germany

In the context of application of drugs containing tamoxifen it is currently still indicated that no interaction between tamoxifen and food is expected or known respectively. Nevertheless we have to assume that food consumed in conventional amounts and containing substances of secondary metabolism and influencing the enzymatic Cytochrome P450 system as well as intestinal transport proteins might cause an interaction with tamoxifen. The influence on the corresponding CYP-isoformes like CYP 2D6 or CYP 3A4 which are especially involved in tamoxifen metabolism should be paid additional attention. The following essay is an attempt to describe the current state of knowledge. Source

Summary Since mid of 2014 Idelalisib is available as a new drug for the treatment of leukemic diseases. Idelalisib is mainly metabolized by aldehyde oxidase (ca. 70 [%]) and to a minor extend by the isoform CYP 3A4 (ca. 30 [%]) to the main metabolite GS-563117. Uridin-5'-diphospho-glucuronosyltransferase 1A4 (UGT 1A4) plays a marginal role in metabolising. According to the accompanying drug information an application can take place without consideration of the diet. Although you should note that some herbal secondary metabolites from the daily diet could definitely affect the metabolism of Idelalisib, even with time-delayed application. Source

Flutamide is an antiandrogen and is primarily metabolized - via isoform CYP1A2 - to 2-hydroxyflutamide, the main metabolite effective with prostate cancer. As well isoenzymes CYP3A4 and CYP2C19 contribute to a minor extent to the metabolism of flutamide 9. A change in CYP1A2 enzyme activity seems to influence the formation of hepatotoxic metabolites after flutamide intake 16. Isoform CYP1A2 shows a high variability in the capacity of metabolism depending on distinct anthropogenic factors and it reacts in reference to its enzyme activity to herbal secondary metabolites as well. Due to an inhibition of isoform CYP1A2, for example after intake of apiaceae vegetables like celery or parsnip, a simultaneous application of flutamide might result in an impairment of metabolism of the antiandrogen. Indol-3-carbinol (ligated to glucose as glucosinolate Glucobrassicin), contained in high concentration in broccoli germs) leads however to an induction of isoenzyme CYP1A2. As well the contamination of the body with polycyclic aromatic hydrocarbons - induced for example by intake of charbroiled meat - could result in an increased de novo expression of isoform CYP1A2 5. This enzyme induction leads to an increased velocity of metabolism. Induction of isoform CYP1A2 seems to decrease the formation of liver-toxic metabolites after flutamide application. Source

Summary food containing linear furanocoumarins (grapefruit, celery, parsnip) might influence the metabolism of tyrosine kinase inhibitors via the inhibition of the intestinal isoform CYP3A4 and of the isoform CYP1A2. Currently only evaluations for two tyrosine kinase inhibitors and only with grapefruit are available. These results provide evidence for a variably strong alteration of pharmacokinetics, respectively. EGCG, contained in green tea, apparently has a synergistic inhibitory effect on tumor growth in therapeutic combination with Erlotinib, whereas the simultaneous application of Sunitinib results in an influence on the pharmacokinetics of tyrosine kinase inhibitor. CYP1A2 mediated metabolism of Erlotinib is influenced by polycyclic aromatic hydrocarbons. Possibly smokers therefore need a higher dose of medication. As well meat being barbecued on char might have some influence due to same reason on the pharmacokinetics of Erlotinib. Compulsory requested is a testing for activating mutations of EGFR (epidermal growth factor receptor)-tyrosine kinase before the application of Erlotinib (mandated since August 2011). Since November 2001 a test for efficacy of Imatinib is mandatory (test for Philadelphia-Chromosom, FISH or PCR). No test is requested for Axitinib and Pazopanib. Regarding the intended safety for therapy via these pre-testings one should critically consider food consumption in case the food could influence metabolising of tyrosine kinase inhibitors via secondary metabolites. For the application of tyrosine kinase inhibitors, which are partly metabolised via isoform CYP1A2, a determination of phenotyp of CYP1A2 could be reasonable, because interaction with secondary metabolites is possible in this context. Nevertheless clinically relevant data are not yet available for the corresponding food. Source

Some saponins and their corresponding aglycones (sapogenins) have been well-known since many years for their effectiveness against leukaemic diseases. Already in the nineties it was shown that asparagus extracts inhibit growth of human leukaemic HL60 cell line. Saponins were identified as effective secondary metabolites (e.g. protodioscin) in Asparagus officinalis L.). The vegetable asparagus (Asparagus officinalis L.) contains numerous saponins, only few kinds of them constitute the main fraction (like protodioscin). In in vitro experiments diosgenin (aglycon of dioscin) showed inhibitory growth effects on human erythroleukaemic cell lines K562 and TIB 180 (HEL). Further experiments with CML cell line KBM-5 proved cytotoxicity as well. Diosgenin was as well effective against HL-60 leukaemic cells. Dioscin - the saponin deriving from diosgenin - as well showed in in vitro experiments an inhibitory effect on the growth of HL-60 leukaemic cells and K562 CML cells (26,28). Protodioscin and the - as sample preparation artefact considered - methyl-protodioscin as well show an inhibitory effect on HL-60 cells. In an experiment with MOLT-4 leukaemic cell lines protodioscin showed already in a less than 2μM concentration a 50 % growth inhibitory effect. As well 25(S)-epimer protoneodioscin proved inhibitory effects on leukaemic cells. Saponins in native vegetable asparagus, likes Dioscin/AS-2-l 25(R,S)-epimer mixture or protodioscin/protoneodioscin 25(R,S)-epimer mixture are predominantly converted into the saponin diosgenin in the gastrointestinal tract. Diosgenin-containing food with their obviously chemo-preventive effects they proved with several cancer diseases have come more and more in the focus as functional food for food industry. So far no clinical relevance of an asparagus meal is proven concerning the effect on leukaemic diseases. The degradation of effective saponins in the gastrointestinal system and bad bio-availability of the considered secondary metabolites put a huge question mark on the benefit the vegetable asparagus as functional food for leukaemic diseases. Source

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