Pharmacokinetics and Pharmacodynamics in Drug Development

The dose-concentration-effect relationship is defined by the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of a drug. Pharmacokinetics comprises all processes that contribute to the time course of drug concentrations 

Pharmaceutical drug development has traditionally been performed in sequential phases, preclinical as well as clinical Phases I to III, in order to answer the two basic questions - which compound should be selected for development, and how it should be dosed. This information-gathering process has recently been characterized as two successive learning-confirming cycles (Fig. 1.4) [8, 9]. The first cycle (traditional Phases I and Ha) comprises learning - in healthy subjects -what dose is tolerated and confirming that this dose has some measurable bene- 

Identification of bio-/ surrogate markers and animal models for efficacy/toxicity 

Dosage form and dosage regimen optimization Integrated information supporting go/no go decision 

For several years, the widespread application of PK/PD concepts in all phases of drug development has repeatedly been promoted by industry, academia, and regulatory authorities [11-16]. Rigorous implementation of PK/PD concepts in drug product development provides a rationale, scientifically based framework for efficient decision-making regarding the selection of potential drag candidates, for 

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Aboagye EO, Price PM, Jones T. In vivo pharmacokinetics and pharmacodynamics in drug development using positron-emission tomography. Drug Discov Today 2001 6 293 02. 

The objective of clinical studies in the pharmaceutical industry is to assess whether a drug candidate will be effective in the treatment of a disease or condition, its risks of unwanted effects, and the relative relationship of these assessments (benefit/risk assessment). These studies must be conducted so that the participating volunteers (healthy subjects or patients) are exposed to the least possible risk consistent with the potential benefit, hi this context, clinical pharmacokinetics and pharmacodynamics in drug development is focused on three main objectives ... 

The Role of Pharmacokinetics and Pharmacodynamics in the Development of Biotech Drugs... 

Meibohm, B., 2006, The role of pharmacokinetics and pharmacodynamics in the development of biotech drugs. In Meibohm, B. (Ed), Pharmacokinetics and pharmacodynamics of biotech drugs Principles and case studies in drug development, Wiley-VCH, 3-13. 

Chen C, Liu X, Smith BJ. Utility of Mdrl-gene deficient mice in assessing the impact of P-glycoprotein on pharmacokinetics and pharmacodynamics in drug discovery and development. Curr Drug Metab 2003 4(4) 272-291. 

P. Chaikin, G. R. Rhodes, R. Bruno, S. Rohatagi, and C. Natarajan, Pharmacokinet-ics/pharmacodynamics in drug development an industrial perspective. J Clin Pharmacol 40 1428-1438 (2000). 

Peck CC. Rationale for the effective use of pharmacokinetics and pharmacodynamics in early drug development. In Yacobi A, Skelly JP, Shah VP, Benet LZ, eds. Integration of pharmacokinetics, pharmacodynamics, and toxicokinetics in rational drug development. New York Plenum 1993. p.1-5. 

Pharmacokinetic/Pharmacodynamic Modeling and Simulations in Drug Development... 

Pharmacogenomics and Genomic Technologies / 2794 Pharmacokinetic/Pharmacodynamic Modeling and Simulations in Drug Development / 2802 Pharmacokinetics Effects of Food and Fasting / 2816... 

Lesko LJ, Williams RL. 1994. Regulatory perspectives the role of pharmacokinetics and pharmacodynamics . In Pharmacodynamics and Drug Development Perspectives in Clinical Pharmacology, Cutler NR, Sramek JJ, Narang PK (eds), 1st edn. John Wiley Sons, Ltd Chichester. 

As discussed earlier, high-affinity anti-drug antibodies produce effects on the pharmacokinetics and pharmacodynamics of drugs in animals and humans. For new therapeutic applications, these effects need to be fully tested in animals before administration to humans. In addition, from a basic science viewpoint, it will be necessary to develop relevant pharmacokinetic and pharmacodynamic models of... 

The role of pharmacokinetics and pharmacodynamics in the decision-making process in drug development and their contribution to the assessment of safety and efficacy of investigational new drugs have been well established. In this chapter, the role of pharmacokinetics and pharmacodynamics is described in terms of current approaches to typical questions or problems, that is, what is done and why. The details of how it is done are constantly evolving and are beyond the scope of this chapter. 

Sheiner LB and Steimer J-L. Pharmacokinetic/pharmacodynamic modeling in drug development. Anna Rev Pharmacol Toxicol 2000 40 67-95. 

The success of any drug delivery system depends upon how it interacts with the biological system to deliver its drug at the optimum rate and at the site where it is needed. This paper discusses some of the considerations that must be made in developing successful drug delivery systems and the opportunities available if a comprehensive assessment is made of the pharmacology, pharmacokinetics, and pharmacodynamics involved. 

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