Pharmacokinetic principles physiological pharmacokinetics

KrishnanK, Andersen ME. 1994. Physiologically-based pharmacokinetic modeling in toxicology. In Wallace Hayes, ed. Principles and methods of toxicology. 3rd edition. New York, NY Raven Press, Ltd. 

LE Gerlowski, RK Jain. Physiologically based pharmacokinetic modeling Principles and applications. J Pharm Sci 72 1103-1127, 1983. 

The therapeutic outcome of topically applied agents used to control oral infections will depend on the characteristics of drugs that take advantage of the unique physiological and anatomical circumstances in the oral cavity. This section is a broad overview of important oral pharmacokinetic principles. 

Knowing the relationship between dose, drug concentration, and effects allows the clinician to take into account the various pathologic and physiologic features of a particular patient that make him or her different from the average individual in responding to a drug. The importance of pharmacokinetics and pharmacodynamics in patient care thus rests upon the improvement in therapeutic benefit and reduction in toxicity that can be achieved by application of these principles. 

Krishnan K, Andersen ME. Physiologically based pharmacokinetic modelling in toxicology. In Hayes AW, ed. Principles and Methods of Toxicology, 5th ed. Florida CRC Press, 2007. 

The explanation of the pharmacokinetics or toxicokinetics involved in absorption, distribution, and elimination processes is a highly specialized branch of toxicology, and is beyond the scope of this chapter. However, here we introduce a few basic concepts that are related to the several transport rate processes that we described earlier in this chapter. Toxicokinetics is an extension of pharmacokinetics in that these studies are conducted at higher doses than pharmacokinetic studies and the principles of pharmacokinetics are applied to xenobiotics. In addition these studies are essential to provide information on the fate of the xenobiotic following exposure by a define route. This information is essential if one is to adequately interpret the dose-response relationship in the risk assessment process. In recent years these toxicokinetic data from laboratory animals have started to be utilized in physiologically based pharmacokinetic (PBPK) models to help extrapolations to low-dose exposures in humans. The ultimate aim in all of these analyses is to provide an estimate of tissue concentrations at the target site associated with the toxicity. 

Figure 5.12 The principle of tiering in risk assessment simple questions can be answered by simple methods that yield conservative answers, and more complex questions require more sophisticated methods, more data, and more accurate risk predictions. PEC = Predicted Environmental Concentration, PNEC = Predicted No Effect Concentration, HI = Hazard Index, CA = Concentration Addition, RA = Response Addition, TEF = Toxicity Equivalency Factor, RPF = Relative Potency Factor, MOA = Mode of Action, PBPK = Physiologically Based Pharmacokinetic, BRN = Biochemical Reaction Network.

Yang RSH, Mayeno AN, Lyons M, Reisfeld B. 2010. The application of physiologically-based pharmacokinetics (PBPK), Bayesian population PBPK modeling, and biochemical reaction network (BRN) modeling to chemical mixture toxicology. In Mumtaz M, editor, Principles and practices of mixture toxicology. Hoboken (NJ) John Wiley Sons. 

It has been reported in an ocular pharmacokinetic study of cyclosporin A incorporated in deoxycholic acid-based anionic and stearylamine-based cationic emulsions in rabbit that, when compared to anionic emulsion, the cationic emulsion showed a significant drug reservoir effect of more than 8 h in corneal and conjunctival tissues of the rabbit eye following topical application [106], Since cornea and conjunctiva are of anionic nature at physiological pH [107], the cationic emulsion would interact with these tissues electrostatically to implicate the observed cyclosporin A reservoir effect. This hypothesis is supported, in principle, by an ex vivo study which showed that cationic emulsion carrier exhibited better wettability properties on rabbit cornea than either saline or anionic emulsion carrier [108],... 

Ubiquitous glycosylated carboxylesterases (CarbE, EC 3.1.1.1), formerly named ali-esterases, are B-esterases belonging to the multigene enzyme superfamily of a/P hydrolases (Hosokawa and Satoh, 2006 Satoh and Hosokawa, 2006). In principle this class of isozymes plays a major role in pharmacokinetics by hydrolytic biotransformation of exogenous ester-drugs and ester-prodrugs. However, their physiological fimction still remains unclear (Satoh and Hosokawa, 2006). 

Krishnan, K., Andersen, M.E. (2001). Physiologically based pharmacokinetic modeling in toxicology. In Principles and Methods of Toxicology (A.W. Hayes, ed.). Chapter 5, pp. 193-241. Taylor and Francis, Philadelphia. 

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