Minimum effective dose

Dose—response relationships are useful for many purposes in particular, the following if a positive dose—response relationship exists, then this is good evidence that exposure to the material under test is causally related to the response the quantitative information obtained gives an indication of the spread of sensitivity of the population at risk, and hence influences ha2ard evaluation the data may allow assessments of no effects and minimum effects doses, and hence may be valuable in assessing ha2ard and by appropriate considerations of the dose—response data, it is possible to make quantitative comparisons and contrasts between materials or between species. 

Misoprostol is a synthetic prostaglandin E2 analog that exogenously replaces prostaglandin stores. The minimum effective dose shown to inhibit acid secretion and promote mucosal defense is 400 meg/day. Misoprostol use is limited by a high frequency of bothersome gastrointestinal effects such as abdominal pain, flatulence, and diarrhea. In placebo-controlled studies diarrhea occurred with twice the frequency in the... 

Both enantiomers and the racemate of l-(3,4-dichlorophenyl)-3-azabicyclo [3.1.0]hexane, 27a-c, have been reported to be in development. The racemate, DOV 216,303, inhibits the reuptake of NE, 5-HT and DA with IC50 values of 20, 14 and 78 nM, respectively [85]. DOV 216,303 is active in tests predictive of antidepressant activity, including the mouse FST (minimum effective dose = lOmg/kg), reversal of tetrabenazine-induced ptosis and locomotor depression. DOV 216,303 was also reported to be well tolerated in phase I clinical trials [85,86], In a phase II study designed to explore safety and tolerability in depressed individuals, patients received either DOV 216,303 (50 mg, b.i.d.) or citalopram (20 mg, b.i.d.) for two weeks [85]. It was found that the side effect profile was not remarkably different between the two treatment groups. In addition, time-dependent reductions in Hamilton Depression Scores (HAM-D) were similar for both groups. 

The (+)-enantiomer, DOV 21,947, is approximately twice as potent at NET and SERT as DOV 216,303. The minimum effective dose in both mouse tail suspension and rat FST models is 5mg/kg [87,88]. The (—)-enantiomer, DOV 102,677, is less potent than DOV 216,303 across all three transporters [89]. It is active in the FST in rats with a minimum effective dose of 20mg/kg. DOV 102,677 is as effective as methylphenidate in reducing the amplitude of the startle response in juvenile mice, without notably altering motor activity. It is reportedly under development for the treatment of alcohol abuse and alcoholism [68]. 

Minimum Effective Dose The minimum effective dose for anthrax, for example, has been stated in the past to be 8,000 to 50,000 spores in aerosol. The new, super-anthrax found in Florida and Washington, D.C., beginning about October 15, 2001, may have a minimum effective dose in spores that is much smaller. 

LCt50 (skin, man) >1500 mg/min3. L irritates eyes and skin and gives warning of its presence. Minimum effective dose (ED min) = 200 mg/m3 (30 min). 

A number of substituted bisindole oxazolidinedione derivatives were prepared using the methods described above (Table VI) (79-81). When examined for their ability to induce a mitotic block in CHO cells, these compounds were active from 2 to 0.002 p.g/ml (Table VII), and compounds having the greatest degree of potency in this in vitro system were evaluated in several experimental tumor systems (Table VIII). The in vitro potency of these compounds appears to correlate with their in vivo potency as reflected by the minimum effective dose that could be administered without toxicity. Several of these compounds were evaluated for their antitumor efficacy when administered by the oral route (Table IX). Compounds 96 and 107 were shown to be exceptionally active in this regard. 

During treatment initiation and dose titration, use 1 hour postprandial plasma glucose to determine the therapeutic response to acarbose and identify the minimum effective dose for the patient. Thereafter, measure glycosylated hemoglobin at intervals of about 3 months. 

Control of gout and hyperuricemia The average dose is 200 to 300 mg/day for mild gout and 400 to 600 mg/day for moderately severe tophaceous gout. Divide doses in excess of 300 mg. The minimum effective dose is 100 to 200 mg/day the maximum recommended dose is 800 mg/day. 

Haloperidol decanoate injection - Individualize dosage and provide close clinical supervision during initiation and stabilization of therapy. The recommended interval between doses is monthly or every 4 weeks. However, variation in patient response may dictate a need for adjustment of the dosing interval as well as the dose. To determine the minimum effective dose, begin with lower initial doses and adjust the dose upward as needed. 

Higher doses are not recommended. Safety and efficacy have not been established for interferon gamma given in doses greater or less than the recommended dose of 50 mcg/m. The minimum effective dose has not been established. 

Postoperative urine retention, atony of bladder PO 10-50 mg 3-4 times a day Minimum effective dose determined by giving 5-10 mg initially then repeating same amount at 1-hr intervals until desired response is achieved. Subcutaneous Initially 2.5-5 mg. Minimum effective dose determined by giving 2.5 mg (0.5 ml), repeating same amount at 15- to 30-min intervals up to a maximum of 4 doses. Minimum dose repeated 3-4 times a day. 

The discussion so far in this section has assumed that the treatment groups are unordered. There are, however, situations where these multiple treatment groups correspond to placebo and then increasing dose levels of a drug. It could still be in these circumstances that we are looking to compare each dose level with placebo in order to identify, for example, the minimum effective dose and again we are back to the pairwise comparisons. 

Clonorchis spp. Chinese liver fluke, occurs in raw fish 0.15 In vitro minimum effective dose... 

Angiostrongylus cantonensis Parasitic worm found in uncooked molluscs, shellfish 2 Minimum effective dose... 

Trichinella spiralis Nematode occurs in raw or inadequately cooked pork 0.3 0-3-1 Minimum effective dose FDA permitted dose to control trichina in pork... 

Toxoplasma gondii Consumption of undercooked meat or poultry or contact with infected animals 0.7 Minimum effective dose for fresh pork... 

Cysticercus bovis Taenia saginata, in man) Tapeworm found in uncooked or undercooked beef causes taeniasis 0.3 Preliminary minimum effective dose... 

The role of dopamine is discussed more thoroughly in Finder, Chapter 14, in this volume. Several antidepressants are thought to have enhanced antidepressant action attributed to extra effects on the dopamine system. Bupropion, which is available as an antidepressant in the United States only, has an indirect effect on dopamine. An appropriate minimum effective dose was not established in the early clinical trial development program, and the rather high doses used in clinical practice may have contributed to the number of reports of convulsions. The rate, which is acceptable at lower doses of 450 mg/day, rises to unacceptable levels at higher doses [J. A. Johnston et al. 1991). 

To overcome some of these limitations, a fixed dose-titration schedule can be implemented in the beginning of a flexible-dose trial in order to reach a minimum effective dose for each patient, followed by a flexible dose-titration schedule. Use of titration points, anchored to a clinical assessment (e.g. forced titration to the next level in the case of Clinical Global Impression severity scores of > 3), makes the titration schedule and the results more homogeneous and tends to unify investigators judgments (for details see Martenyi et al 2002). 

At doses >0.5 mg/kg BW, paraquat produced a dose-dependent avoidance of foods the ED50 for conditioned taste aversion was 2.4 mg/kg BW (minimum effective dose was 0.78 mg/kg BW) none of these doses produced overt clinical or histological signs of toxicity (Dey etal. 1987)... 

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