Hepatic drug-metabolizing

Sriram K, Misra UK. 1983. Interaction of endosulfan and dietary vitamin A on rat hepatic drug metabolizing enzymes. Acta Vitaminol Enzymol 5 213-218. 

Each plant tissue tends to have an obviously distinctive profile of flavonoids. The flavonoid content can reach about 0.5% in pollen, 10% in propolis, and about 6 mg/kg in honey. Havonoid aglycones appear to be present only in propolis and honey, while pollen contains flavanols in herosidic forms. The flavonoids in honey and propolis have been identified as flavanones and flavanones/flavanols (Campos et ah, 1990). The antimi-crobially active flavanone pinocembrine was foimd to be a major flavonoid in honey (Bogdanov, 1989). Amiot et ah (1989) studied two blossom and two honeydew Swiss honey samples and foimd that pinocembrine was the main flavonoid. Pinocembrine concentration varied between 2 and 3 mg/kg (Bogdanov, 1989). Berahia et ah (1993) analyzed sunflower honey samples and detected six flavone/flavols, four flavanone/ flavols, and pinocembrin, of which pinocembrin is the main flavonoid. The flavonoids in sunflower honey and propolis were characterized and assessed for their effects on hepatic drug-metabolizing enzymes and benzo [fl]pyrene-DNA adduct formation (Sabatier et ah, 1992 Siess et ah, 1996). 

Siess, M. H., Le Bon, A. M., Canivenc-Lavier, M. C., Amiot, M. ]., Sabatier, S., Yaubert, S. Y., and Suschetet, M. (1996). Flavonoids of honey and propolis Characterization and effects on hepatic drug-metabolizing enzymes and benzoja] pyrene-DNA.. Agric. Food Chem. 44, 2297-2301. 

Goldberg AM, Meredith PA, Miller S, et al. 1978. Hepatic drug metabolism and heme biosynthesis in lead-poisoned rats. Br J Pharmacol 62 529-536. 

Cytochrome P-450 A superfamily of isoenzymes principally involved in hepatic drug metabolism. 

Moore, L.B., Goodwin, B., Jones, S.A., Wisely, G.B., Serabjit-Singh, C.J., Willson, T.M., Collins, J.L. and Kliewer, S. A. (2000) St. John s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proceedings of the National Academy of Sciences of the United States of America, 97, 7500-7502. 

Campbell MA, Gyorkos J, Leece B, et al. 1983. The effects of twenty-two organochlorine pesticides as inducers of the hepatic drug-metabolizing enzymes. Gen Pharmacol 14(4) 445-454. 

Hodgson E, Kulkarni AP, Fabacher DL, et al. 1980. Induction of hepatic drug metabolizing enzymes in mammals by pesticides A review. J Environ Sci Health B 15(6) 723-754. 

Dent, J.G., Netter, K.J.. and Gibson, J.E. Effects of chronic administration of polybrominated biphenyls on parameters associated with hepatic drug metabolism. Res. Commun. Chem. Pathol. Pharmacol. (1976) 13 75-82. 

Nolin TD, Erye RF, Matzke GR (2003) Hepatic drug metabolism and transport in patients with kidney disease. Am J Kidney Dis 42(5) 906-925... 

Cheadwick RW, Copeland MF, Carlson GP, et al. 1988. Comparison of in vitro methods for assessing the effects of carbon tetrachloride on the hepatic drug-metabolizing enzyme system. Toxicol Lett 42 309-316. 

Day WW, Weiner M. 1991. Short communications Inhibition of hepatic drug metabolism and carbon tetrachloride toxicity in Fisher-344 rats by exercise. Biochem Pharmacol 42 181-184. 

However, the physiology of ageing includes poorer gastrointestinal absorption, somewhat reduced hepatic drug metabolism, and, commonly, a loss of lean body mass. While all of these have been documented, none is of as great a significance as the loss of renal excretory function which is invariably present in old age. 

It must be recognized that developmental differences in hepatic drug metabolism occur consequent to reductions in the activity of specific drug-metabolizing enzymes and their respective isoforms. For most enzymes, the greatest reduction of activity is seen in premature infants where immature function may also reflect continued organogenesis. This... 

Il.b.l.1. Adverse effects of anti-secretory treatment. Histamine H2 antagonists and proton pump inhibitors are very safe as well as effective treatments. Cimetidine has small effects on hepatic drug metabolism which are only of clinical signiflcance with drugs used in doses close to toxic levels, notably phenytoin, aminophylline and warfarin. Other adverse effects such as headache, rash and thrombocytopenia are rare. 

The reduction in therapeutic effectiveness that can occur when antihistamines are given for long periods is probably related to an induction of hepatic drug-metabolizing enzymes. Children tend to eliminate antihistamines more rapidly than adults, while individuals with hepatic impairment may eliminate them more slowly. 

Renton, K.W. (2000) Hepatic drug metabolism and immunostimu-lation. Toxicology 17 142 173-178. 

Age In newborn infants, the glomerular filtration rate and tubular transport is immature, which takes 5 to 7 months to mature. Also, the hepatic drug metabolism capacity is also inadequate (that is why chloramphenicol can produce grey baby syndrome ), and due to the higher permeability of blood brain barrier, certain drugs attain high concentration in the CNS. 

Moore LB, Goodwin B, Jones SA, et al. St. John s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA 2000 97 7500-7502. 

The liver is the principal site of drug metabolism. Hepatic drug metabolism is usually classified into two distinct phases. Phase I reactions are oxidation, reduction or hydrolysis. One of the most important systems that catalyse oxidation are the haem-containing cytochrome P-450 enzymes. 

Interactions involving changes in the activity of hepatic drug-metabolizing enzyme systems have been discussed (see also Chapters 4 and 66). 

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