Drug distribution definition

Many departments have moved pharmacists from the central pharmacy to patient care areas with the expectation that they will provide pharmacy care automatically. These relocated pharmacists are expected to define their roles without a sense of a departmental mission. Without a clear definition of clinical services and without the use of a mission statement that reflects this definition in actual practice, pharmacists are placed in an ambiguous situation. They have the desire to care for patients but do not clearly understand the priorities. The immediacy of drug distribution may... 

The generalist and the specialist models have been successful in many hospitals, provided that there has been a systematic approach to the development, implementation, and evaluation of the clinical services provided. There must be a clearly articulated philosophy of practice that describes why a pharmacist provides clinical services and a clear definition of the work to be done. We must remember that the patient is central to any endeavor. If the clinical service is defined in terms of patient need, it becomes easier to define priorities, resource requirements, and optimal outcomes. The primary focus of a clinical service should be the patient and not a medical service or a drug category. Full integration of clinical practice into drug distribution services optimizes the chances for success. 

Volume of distribution is a conceptual pharmacokinetic parameter that scales the extent of a drug distributed into the tissues. A well-known parameter, elimination half-life, can be derived from clearance and volume of distribution. It is a very important developability criterion that warrants the desired dose regimen. It should be noted here that half-life must be discussed in the context of a biologically relevant concentration. A purely mathematically derived half-life is sometimes biological irrelevant. Some more definitive explanations and comprehensive discussion of the major pharmacokinetic parameters and their biological relevance have been extensively reviewed.25,26 These parameters should be examined across several different preclinical species to predict the behavior in humans. The DMPK topics will be discussed in Chapters 5 and 6. 

Williams, RL. and Riviere, J.E., 1989a, Definition of a physiologic pharmacokinetic model of cutaneous drug distribution using the isolated perfused porcine skin flap (IPPSF), J. Pharm. Sci., 78 550-555. 

With respect to the definition of the term in the denominator represents in fact that part of the drug-distribution volume which is totally cleared from the drug per unit of time. It is easy to recognize that such a relationship offers an opportunity of estimating the total (plasmatic) clearance. The estimation may be made according to the formula ... 

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

A general definition of log P and log D, in its simplest form, can be given as the logarithm of the ratio (P or D) of the concentration of species of interest (the drug in a pharmaceutical context) in each phase, assuming the phases are immiscible and well separated prior to analysis. P is defined as the partition coefficient, whereas D is the distribution coefficient. However, the simplest form does not reveal some of the intricacies of the determination and use of these parameters, and further explanation is necessary. 

Clearance (Cl) and volumes of distribution (VD) are fundamental concepts in pharmacokinetics. Clearance is defined as the volume of plasma or blood cleared of the drug per unit time, and has the dimensions of volume per unit time (e.g. mL-min-1 or L-h-1). An alternative, and theoretically more useful, definition is the rate of drug elimination per unit drug concentration, and equals the product of the elimination constant and the volume of the compartment. The clearance from the central compartment is thus VVklO. Since e0=l, at t=0 equation 1 reduces to C(0)=A+B+C, which is the initial concentration in VI. Hence, Vl=Dose/(A+B-i-C). The clearance between compartments in one direction must equal the clearance in the reverse direction, i.e. Vl.K12=V2-k21 and VVkl3=V3-k31. This enables us to calculate V2 and V3. 

The severe conditions that may be encountered during distribution can be covered by stress testing of definitive batches of drug substance. 

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