Effective drug concentration

There have been a number of recent preclinical studies that highlight the importance of plasma protein binding when making cross-species comparisons, interpreting drug concentrations in various compartments, and determining effective drug concentrations at the site of action. 

Empirically it is known that effective drug concentrations are needed for at least 3 parasite-life cycles (=6 days) to obtain cure without recrudescence. By combining a drug with a fast action but short half life such as artemether and an agent with a slow action and long half life the treatment course can be short (2-3 days) which will benetit compliance, the patients condition will improve fast and resistance-development might be delayed. 

Animal data serve as the springboard to estimating a safe and effective range of doses for human therapeutic purposes. Initial doses in phase 1 studies are based on preclinical pharmacokinetic and safety data. First estimates of safe and effective drug concentrations in plasma in human studies are also based on animal data. The Clinical Studies section in the product label includes information derived from tolerance studies of the drug (phase I), pivotal human data demonstrating efficacy at a defined dose or dose range, and a description of untoward effects observed in... 

Therapeutic window The range of drug concentrations in the body that will promote optimal beneficial effects. Drug concentrations less than the lower end of this range will be ineffective, and concentrations greater than the upper end of this range will create excessive side effects. 

Due to the accessibility of the eye surface, topical administration of ophthalmic medications is the most common method for treating conditions affecting the exterior eye surface. However, the unique anatomy and physiology of the eye renders it difficult to achieve an effective drug concentration at the target site. Therefore, efficient delivery of a drug past the protective ocular barriers accompanied with minimization of its systemic side effects remains a major challenge. 

An ideal ophthalmic delivery system should be able to achieve an effective drug concentration at the target site for an extended period of time while minimizing systemic side effects. In addition, the system should be comfortable and easy to use, as the patient s acceptance will continue to play an important role in the design of future ocular formulations. 

Fig. 3. Pharmacodynamics of drug response. (A) Relationship between the number of receptors and drug response, where lA is a low number, and IB is a high number of receptors. (B) Relationship of drug response to affinity of receptors, where 2A is a high affinity receptor, and 2B is low affinity. The 50% effective drug concentration C2A is lower for a high-affinity receptor compared with concentration C2B. From Weber W. Human drug response. In Bobrow M, Harper PS, Scriver C, et al, editors. Pharamcogenetics. New York Oxford University Press 1997. p. 28 with permission.)...

Passive diffusion involves transfer of drug molecules from a region of high concentration to a region of low concentration, with the driving force being the effective drug concentration on one side of membrane. Pick s law mathematically describes the process. The equation can be written as. 

Cho, Y, Kim, W.S., Hur, G.H., et al., 2012. Minimum effective drug concentrations of a transdermal patch system containing procyclidine and physostig-mine for prophylaxis against soman poisoning in rhesus monkeys. Environ. Toxicol. Pharmacol. 33, 1-8. 

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