Minimum effective concentration

Fig. 1. Blood—drug concentration curve used to determine bioavailabiLitv and bioequivalence. C is the maximum dmg concentration in the blood and corresponds to some The AUC (shaded) represents the total amount of orally adininistered dmg the time from points A to B represents dmg onset, from points B to D, the duration MEC = minimum effective concentration MTC = minimum toxic concentration and TI = therapeutic index.

Dtug interactions can cause serious problems in clinical practice especially when the affected dmg has the potential to be highly toxic. Furthermore, pharmacokinetic interactions are clinically important if the affected dmg has a narrow therapeutic range (i.e. small difference between the minimum effective concentration and the toxic concentration Fig. 1) and a steep concentration-response curve (i.e. significant alterations in pharmacological and/or adverse effects caused by small changes in blood concentration). 

Response fluctuations occur with disease progression as the patient s dopamine reserves are depleted in the brain and as a complication of PD treatment. Motor fluctuations include delayed peak response, early wearing off, random unpredictable on-off, and freezing. Dyskinesias include chorea, dystonia, and diphasic dyskinesia. Wearing off can be visualized by imagining the therapeutic window of dopamine narrowing over time. The therapeutic window is defined as the minimum effective concentration of dopamine required to control PD symptoms (on without dyskinesia) and the maximum concentration before experiencing side effects from too much dopamine (on with dyskinesia). Early in the disease, a dose of... 

QL can be also determined as the lowest concentration of the analyte in which duplicate injections have RSD values less than or equal to 2%. For clinical applications, QL should be at least 10% of the minimum effective concentration [2], and it should always be within the linear working range [3]. 

Figure 12.1 shows the plasma concentration versus time profile of an orally administered hypothetical drug. When the drug concentration in plasma equals the minimum effective concentration (MEC), therapeutic response is initiated. When the concentration exceeds the minimum toxic concentration (MTC), the drag causes toxic responses. Therefore, for ideal therapeutic response, the plasma concentration of drugs should be between the MEC and MTC. This region is called the therapeutic window. In Figure 12.1 the MEC is 1.5 ng/ mL, and the MTC is 3.5 ng/mL. The therapeutic window is between 1.5 and 3.5 ng/mL. 

If the minimum effective concentration is 3 mg/mL, what is the onset, intensity, and duration of action of the administered drug for which the following plasma concentration versus time data is available ... 

Spermicidal effectiveness (Sander-Cramer Assay [sperm dilution and minimum effective concentration (MEC)] [45]... 

A series of DCE-based formulations containing Igepal CO-630 Special (N9) and dextran sulfate (DS) were evaluated for in vitro contraceptive testing. Also included in the screening tests were placebos, N9, two commercial spermicidal products (Conceptrol and KY Plus), vaginal moisturizer products (KY Jelly and Replens ), and saline. Test results are summarized in Table 6. The N9-containing products exhibited similar spermicidal activity, as illustrated by the minimum effective concentration (MEC). Samples without N9 did not have spermicidal activity. DCE placebo vehicle inhibits sperm penetration into the cervical mucus, illustrated by the very low MOET values after 1 10 and 1 160 dilutions. This activity has not been reported for anionic or nonionic polymer vehicles. There are no striking differences... 

Pondweed, Potamogeton tricarinatus 4000 pg/L 1 -h exposure in irrigation canal Minimum effective concentration 5... 

Fig. 1.4. 5 Shows the administration of 2nd dose between the 7-8 hours interval which maintains the drug plasma levels above minimum effective concentration.

In a concentration range higher than those exhibiting repetitive responses, this class of compounds blocks the nerve conduction. We have also determined neuro-blocking activity in terms of the minimum effective concentration (MBC in M) in the saline solution 76). In contrast to effect on excitatory activity, substituent effects... 

Figure 1 Comparison of typical pharmacokinetic profiles seen for conventional versus controlled release formulations. Abbreviations. MEC, minimum effective concentration MTD, maximum tolerable dose.

Narrow Therapeutic Index Drugs Drugs having, for example, less than a two-fold difference in the minimum toxic concentrations and the minimum effective concentrations (21 CFR 320.33 (c)). 

Similarly, the peaks between doses should not exceed toxic levels. Together, the minimum effective concentration and toxic level define the therapeutic window of the drug. 

PROBLEM An oral drug has a dose of 500 mg, oral bioavailability of 80%, Vd of 70 L, kel of 0.3 h 1, and fcab of 0.8 IT1. The drug has been prescribed to be taken every 4 hours. If the minimum effective concentration of the drug is 1.5 /xg / ml., will the patient still have an effective concentration of the drug when the second dose is administered ... 

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