Potency and Efficacy

Essentials of Toxic Chemical Risk Science and Society 

In the context of toxic chemicals, efficacy refers to the maximum frequency of a specified toxic effect. For example, one chemical may produce a toxic effect in 100% of an exposed population, while a second chemical produces the same toxic effect, but only in 65% of the population. The second toxic chemical is then said to be less efficacious than the first. The concept of efficacy, like potency, is more awkward when applied to toxic chemicals than therapeutic drugs. The persistence of these terms is a reminder that toxicology grew out of the field of medical pharmacology fairly recently, less than a century ago. 

Two concepts that at this stage should not present us with any difficulty are the potency and efficacy of a dmg. The potency is a function of the amount of drug required for its 

When an antagonist binds irreversibly to the receptor site, thus producing either permanent chemical changes or inactivation of the receptor site, or both, this is referred to as noncompetitive 

FIGURE 1.8 a) I) i h yd ro m orpin no ne is more potent is a competitive antagonist at adrenergic receptors. 

FIGURE 1.9 a) Atropine is a competitive antagonist at cholinergic receptors, b) Phenoxybenzamine is a noncompetitive antagonist at adrenergic receptors. 

FIGURE 1.11 a) The concept of antagonism or potentiation of pharmacologic effects, b) Drugs with higher therapeutic indices are safer. TI = therapeutic index, LD50 = median lethal dose, ED50 = median effective dose. 

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Test reports and research data sufficient to establish purity, safety, potency, and efficacy of the product... 

Real-time spectroscopic methods can be used to measure the binding, dissociation, and internalization of fluorescent ligands with cell-surface receptors on cells and membranes. The time resolution available in these methods is sufficient to permit a detailed analysis of complex processes involved in cell activation, particularly receptor-G protein dynamics. A description of the kinetics and thermodynamics of these processes will contribute to our understanding of the basis of stimulus potency and efficacy. 

Of the direct methyl group replacements reported, small groups such as hydroxymethyl and fluoromethyl are tolerated, while larger groups in this position result in compounds with reduced in vivo potency and efficacy. The n-butyl derivative (159) was the only C9 methyl replacement analogue that showed a marked effect on hypothermia (5°C decrease at 168/rmol/kg ED50 not calculated) [116]. 

Looking at the downstream processing of recombinant pharmaceutical proteins from different sources as a whole, there are more common steps than operations addressing expression system-specific problems or requirements. One of the most important common features is that a given end product must meet the same standards and specifications in terms of safety, quality, potency and efficacy, regardless of the production host. Furthermore, the physicochemical properties of such end products should be identical, so that the intrinsic features used for purification (affinity, hy-drophobicity etc.) are the same. Well-established procedures and protocols should therefore be utilized, and should be adapted to the special requirements of the source material only when absolutely necessary. This is particularly true in the case of pharmaceuticals, since the tendency in this field is to stick to established methods... 

Among aliphatic substituents, the pentyl side chain was found to be optimal for both in vitro potency and efficacy. Derivative 5b (R5 = OH, R9 = M-pentyl) is a full agonist in the LMMP-GPI model (90% of the maximum efficacy of serotonin ... 

Increasing the size of the ether substituent (5i) led to a further increase in potency and efficacy in vitro. However, this improvement in vitro, which might be accounted for by secondary lipophilic interactions, did not improve efficacy in vivo. Substitution at the 5-position of the indole nucleus by larger polar or lipophilic substituents (5j) abolished activity in vitro. 

Further tests are carried out to evaluate the potency and specificity of the isolated lead compounds. This is usually followed by modifications of the compounds to improve properties through synthesis of variations to the compounds via chemical processes in the laboratory and frequently with modifications to the functional groups. The optimized lead compounds go through many iterative processes to keep improving and optimizing the drug interaction properties to achieve improved potency and efficacy. 

El-Sankary, W Gibson, G.G., Ayrton, A. and Plant, N. (2001) Use ofa reporter gene assay to predict and rank the potency and efficacy of CYP3A4 inducers. Drug Metabolism and Disposition The Biological Fate of Chemicals, 29, 1499-1504. 

For a pair of chemicals, the one that is less bioavailable, less bioaccumulative, less reactive, is cleared more thoroughly and quickly, and interacts with fewer disease-related target molecules (receptors, enzymes, DNA, etc.) with lower potency and efficacy, will have the lower inherent toxicity. 

The remainder of the chapter is organized into sections dealing with each of the five components (bioavailability, bioaccumulation, reactivity, clearance, and interaction potency and efficacy) required to assess differential toxicity. The first four are subjects of recent reviews so they are treated only briefly, to the level required for understanding how to perform a final integrated differential toxicity assessment. The final component of specific chemical-target interactions is treated in more depth. Final sections deal with integration of these different streams of information. 

NSAIDs and COX-2 inhibitors show good potencies and efficacies in mild to moderate pain conditions and in inflammation. Many combinations of NSAIDs with other principles are on the market or under development. Misoprostol (on the market) and NO donors (under development) reduce the side-effects of NSAIDs on the gastric mucosa and opioid analgesics (standard WHO ladder of pain treatment) add to the analgesic potency of NSAIDs. 

The inappropriate or illegal use and abuse of narcotics such as heroin is a major problem in many countries. Hence, various strategies have been employed to treat people who are addicted to heroin and other opioids. Methadone is the primary pharmacological intervention used to treat opioid addiction. Methadone is a strong opioid agonist, similar in potency and efficacy to morphine. While giving an opioid to treat an opi-... 

During the first half of the century, there was virtually an exclusive reliance on animal testing as the primary model for drug discovery and development. New chemical entities were administered to rodents in the primary screen assay, and the appropriate responses were monitored for indications of therapeutic potential. Compounds meeting the appropriate potency and efficacy criteria were promoted to more diverse and sophisticated animal models to characterize their pharmacological profile. The responses that were monitored included blood pressure (hypotensives), latency to respond to painful stimuli (analgesics), attenuation of seizure propensity (antiepileptics) and other responses that were intuitively and pharmacologically valid indicators of medicinal potential or toxicity. Some of these methods were semiautomated and quite sophisticated for their time, particularly for cardiovascular indications [1]. 

Typical dose response curve for drugs showing differences in potency and efficacy. EDS0 drug dose that shows 50% of maximal response. 

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