Hepatitis drugs

A special case for reduced bioavailabilty results from first-pass extraction that sometimes might be subjected to saturable Michaelis-Menten absorption kinetics. The lower the hepatic drug clearance is (Clhep) in relation to liver blood flow (Ql), or the faster the drug absorption rate constant (Ka), and the higher the dose (D) are, the more bioavailable is the drug (F). 

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. 

KS Pang, M Rowland. Hepatic clearance of drugs. I. Theoretical considerations of a well-stirred model and a parallel tube model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J Pharmacokin Biopharm 5/6 625-653, 1977. 

The mass transfer coefficients may also be expressed in units of time-1 by multiplying by the appropriate compartmental volume term. Irreversible drug elimination from the tissue requires the addition of an expression to the differential equation that represents the subcompartment in which elimination occurs. For instance, hepatic drug elimination would be described by a linear or nonlinear expression added to the intracellular liver compartment mass balance equation since this compartment represents the hepatocytes. Formal elimination terms are given below for the simplified tissue models. 

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. 

Brandon, E.F., Raap, C.D., Meijerman, I. etal. (2003) An update on in vitro test methods in human hepatic drug biotransformation research pros and cons. Toxicology and Applied Pharmacology, 189 (3), 233-246. 

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

Peggins, J., Shipley, L. and Weiner, M. (1984). Characterization of age-related changes in hepatic drug metaholism in miniature swine. Drug Metab. Dispos. 12 379-381. 

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. 

Lamartiniere CA, Nicholas JM. 1984. Neonatal chlordecone alteration of the ontogeny of sex-differentiated hepatic drug and xenobiotic metabolizing enzymes. Biochem Pharmacol 33(24) 4092-4095. 

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... 

Neural networks are a relatively new tool in data modelling in the field of pharmacokinetics [54—56]. Using this approach, non-linear relationships to predicted properties are better taken into account than by multiple linear regression [45]. Human hepatic drug clearance was best predicted from human hepatocyte data, followed by rat hepatocyte data, while in the studied data set animal in vivo data did not significantly contribute to the predictions [56]. 

Investigation of potential adverse interactions with drugs likely to be co-prescribed with the test drug may also be required. A generalised approach, such as the determination of effects on hepatic drug metabolising enzymes, may be sufficient, but in most cases, a number of drug-specific interaction studies will also be required. 

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. 

Microsomal enzyme function may also be depressed in heart failure and hepatic drug clearance reduced leading to elevated Cp of drugs cleared in this way. 

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. 

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