Basic Pharmacokinetics

Once injected into the eye, antibiotics diffuse through the vitreous cavity and are eliminated by either a posterior or an anterior route (23 25). Several factors govern the intravitreal concentration of an antibiotic at any given time. The initial concentration is a result of the extended distribution and the initial dose. Subsequently, the volume of distribution, the dose of the initial injection, and the rate of elimination govern the concentration of the drug at a given time (26). Two parameters characterize the elimination phase of the drug (i) the elimination half-life and (ii) the apparent volume of distribution. 

The volume of distribution is a measure of the extent of physical distribution of the drug, but corresponds to the physical volume only rarely. Volume of distribution may be lower or many times higher than the actual physical volume, depending on 

Drag Model Dose Phakic Aphakic Aphakic vitrectomized References 

The rate constant k is of first order with a dimension of time (1). The elimination constant defines the fractional rate of drug removal and is equivalent to the rate of elimination divided by the amount of drug in the compartment. Given this definition, the half-life is thus Tx/2 = 0.693 divided by k. 

Clearance is the parameter that relates the drug concentration in a cavity to the rate of its elimination. Clearance multiplied by concentration equals the rate of elimination. Units of clearance are expressed in volume per unit of time. The half-life is then expressed as T /2 (0.693 x volume of distribution)/clearance. The half-life 

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Pharmacokinetics. All subchronic and chronic toxicity studies now incorporate (either in the study itself or in a parallel study) evaluation of the basic pharmacokinetics of a compound. This is discussed in detail in Chapter 18. 

Ritschel WA, Kearns GL. Handbook of basic pharmacokinetics. .. including clinical applications. 6th ed. Washington (DC) American Pharmaceutical Association 2004. 

Fig. 1. Developmental changes in body water and fat content (from Ritschel WA and Kearns GL, 1999, reproduced by permission from the Handbook of Basic Pharmacokinetics, 5th edn. 1999 by the American Pharmaceutical Association).

DRUG CONCENTRATION-TIME PROFILES AND BASIC PHARMACOKINETIC PARAMETERS... 

The scientific basis of a compound is sound and its basic pharmacokinetic... 

Jones DR, Hall SD. Mechanism based inhibition of cytochrome P450 in vitro kinetics and in vitro-in vivo correlations. In Rodrigues AD, ed. Drug-Drug Interactions From Basic Pharmacokinetics Concepts to Marketing Issues. New York, NY Marcel Dekker, 2001. 

ALEXANDER L.RAKHMILEVICH AND GEORG WIDERA Basic pharmacokinetics of oligonucleotides and genes... 

Drugs are typically tested in animals initially, often using several different species. Initial information on the basic pharmacokinetic and pharmacodynamic properties of the compound is obtained. Information on dosage and toxicity is also obtained from these animal trials. 

Ciccone CD. Basic pharmacokinetics and the potential effect of physical therapy interventions on pharmacokinetic variables. Phys Ther. 1995 75 343-351. 

In addition to knowledge about the clinical efficacy, adverse effect profile, and likelihood of emergence of resistance, the physician caring for an HIV-infected patient must be well versed in basic pharmacokinetics as well. Such patients are frequently taking multiple medications, including combinations of antiretroviral agents, prophylaxis or treatment for opportunistic infections, and opioid pain medications or methadone for maintenance therapy. 

Dhillon, S. and Gill, K., 2006, Basic pharmacokinetics. In Dhillon, S. and Kostrzewski, A. (Eds), Clinical pharmacokinetics, Pharmaceutical Press, 1-44. 

Simplistic models with few rules have proven to be highly beneficial in predicting basic pharmacokinetic properties without extensive computational analysis. The Lipinkski rule of 5 for predicting which compounds are likely to show good or poor absorption properties is one example that has found wide application in industry and there are others. Egan et al. (2000) reported that compounds possessing a PSA of <148.1A2 and log Kow above 5.88 would be poorly absorbed. Veber et al. (2002) proposed a simple classification system for oral bioavailability, where compounds... 

The basic pharmacokinetic parameters of organic nitrovasodilators, including the time of onset (with favored routes of administration) and duration of action are summarized in Tab. 10.1. 

Strongly acidic, pH of 3-5 is weakly acidic, pH of 6-8 is neutral, pH of 9-11 is weakly basic, and pH of 12-14 is strongly basic Pharmacokinetics A term suggesting the quantitative uptake of drugs by the body biotransformation, distribution, metabolism, and excretion from the body of animals or humans... 

Basic pharmacokinetic/dynamic information can be found in a number of common sources such as the BNF, the SPC for the drug (or equivalent data if outside the UK), Martindale The Complete Drug Reference and AHFS Drug Information [1,3,4]. There are other books, such as Therapeutic Drugs, edited by C. Dollery, which may give more detailed information [2]. Other useful sources include online pharmacy and medical databases, bibliographic databases to identify relevant published material, and pharmaceutical manufacturers. 

After the basic pharmacokinetic parameters are known, the tests are repeated with volunteers that take other medication or eat different diets to see whether these parameters influence the pharmacology of the new drug. 

Despite these technical advances, adverse reactions still occur frequently with digoxin, phenytoin, and many other drugs for which drug concentration measurements are routinely available. The persistence in contemporary practice of dose-related toxicity with these drugs most likely reflects inadequate understanding of basic pharmacokinetic principles. This is illustrated by the following case history (5) ... 

Other concerns have been expressed. ° These include the observation that vehicle components of the products to be evaluated may have different effects on the adhesive properties of the tape. In addition, it is important to appreciate that because the dermatopharmacokinetic bioequivalence studies will most likely be carried out on normal disease-free human volunteers, the generated data may show little resemblance to the actual drug distribution within the stratum corneum of patients. Non-etheless, following further validation, the technique will have several advantages. For example, basic pharmacokinetic parameters, such as AUC, Craax, max, Tud half-Hfc, may be approximated from the data obtained. In addition, the approach could be applicable to all types of topical preparation. 

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