Metabolism, pharmacokinetic

Bertz, R.J. and Granneman, G.R. (1997) Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clinical Pharmacokinetics, 32 (3), 210-258. 

Through scientific procedures or through experience based on common use in food if used in food prior to 1958. FEXPAN uses the same criteria described above to conduct GRAS assessments namely, exposure, natural occurrence, chemical identity, structure-activity relationships, metabolism, pharmacokinetics, and toxicity data. 

Blume HH, Schug BS. Biopharmaceutical characterization of herbal medicinal products are in vivo studies necessary Eur J Drug Metabol Pharmacokinet 2000 25 41—48. 

K. Hosoya, M. Tomi, M. Takayama, Y. Komokata, D. Nakai, T. Tokui, K. Nishimura, M. Ueda, M. Obinata, S. Hori, S. Ohtsuki, G. L. Amidon, and T. Terasaki. Transporter mRNA expression in a conditionally immortalized rat small intestine epithelial cell line (TR-SIE). Drug Metabol. Pharmacokinet. 19 264-269 (2004). 

As mentioned above, bioavailability is the degree to which a drug reaches the intended site of action. The amount of drug that reaches systemic circulation will depend on the processes of absorption, distribution, and biotransformation (when the route of administration exposes the drug to first-pass metabolism). Pharmacokinetics are often linear and when they are nonlinear it is often due to a saturation of protein binding, metabolism, or active renal transport. 

Wojcicki J, Sulikowski T, Wojcicki M, Drozdzik M, Gawronskaszklarz B, Barcewwisz-niewska B, Skowron J, Rozewicka L, Goldyn U (1995) Eur J Drug Metabol Pharmacokinet 20 119... 

A comprehensive knowledge of all the preclin-ical information about a compound is an essential requirement for the safe conduct of the first study in man. Toxicology, metabolism, pharmacokinetics and pharmacodynamics are all important despite their limited predictive power for man. As explained above, the study design must take the findings into account. 

Variability in metabolism A subset (approximately 7%) of the population is devoid of CYP2D6, the enzyme responsible for the formation of the 5-hydroxymethyl metabolite of tolterodine. The identified pathway of metabolism for these individuals ( poor metabolizers ) is by dealkylation via cytochrome P450 3A4 (CYP3A4) to A/-dealkylated tolterodine. The remainder of the population is referred to as extensive metabolizers. Pharmacokinetic studies revealed that tolterodine is metabolized at a slower rate in poor metabolizers than in extensive metabolizers this results in significantly higher serum concentrations of tolterodine and in negligible concentrations of the 5-hydroxymethyl metabolite. 

Because rivastigmine is not hepatically metabolized, pharmacokinetic cytochrome P450-related drug interactions are not expected. However, the previously discussed pharmacodynamic interactions associated with other cholinesterase inhibitors may occur with rivastigmine as well. 

In contrast to penetrating radiation, which passes through tissue in a weU-known manner, or even with the more complex situations arising fiom nonuniform distributions of internally deposited radionuclides, dosimetry of chemicals is far more difficult. Factors requiring consider ation in chemical dosimetry include the type of chemical under consideration, dose, duration of exposure, route of administration, aU possible metabolic pathways, capacity of the chemical to affect its own metabolism, pharmacokinetics, rate of excretion, and dose to the biological target at sites of tumor formation (which may vary depending on the route of administration). 

Bauerova K, Matusova D, Kassai Z. Chemical enhancers for transdermal drug transport. Eur J Drug Metabol Pharmacokinet 2001 26 84-94. 

Hadgraft J. Recent developments in topical and transdermal delivery. Eur J Drug Metabol Pharmacokinet 1996 21 165-173. 

The assessment of human cancer risk associated with a substance is a complicated scientific endeavor requiring careful review of all pertinent information by professionals. Such assessment involves primarily the evaluation of clinical, epidemiological, and animal studies as well as short-term tests, structure activity, comparative metabolism pharmacokinetics, and mechanism of action when possible. 

Baillie, T. A. 1992. Advances in the application of mass spectrometry to studies of drug metabolism, pharmacokinetics and toxicology. Int. J. Mass Spectrom. Ion Proc., 118/119, 289-314. 

W.H. Braun, G.E. Blau, and M.B. Chenoweth, The metabolism/pharmacokinetics of pentachlorophenol in man, and a comparison with the rat and monkey, in W.E. Deichmann, ed., Toxicology and Occupational Medicine, New York, Amsterdam, Oxford, Elsevier/North-Holland, 289, 1992. 

The in vivo mammalian micronucleus test is used to assess the mutagenic hazard in consideration of factors like in vivo metabolism, pharmacokinetics and DNA-repair processes, although these may vary among species and among tissues. This assay is an important part of the gentox testing battery, applied for pharmaceuticals and chemicals. 

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