I want to test the effect of a neuroprotective drug on rotenone rat model of Parkinson's disease but after reading the related articles about my work, I became doubts about select the best dosage of the drug and treatment methods. in some of the articles they using a low dosage of a neuroprotective drug and in some high dosage and their treatment was different in some cases, they use the oral method and some intraperitoneal injection method.
Does anyone have any suggestions to select the best dosage and treatment (o.p or i.p)?
Many thanks
Do you know the highest dose that does not produce an adverse effect in you model? If so, this is your NOAEL. A dose at least 10 fold lower (ideally 100 fold) than the NOAEL should be your maximum dose to obtain a minimum margin of safety with a good therapeutic index. You will then need to use this dose as a starting point for a dose response analysis to assess for an effective dose that improves function/reduces pathology. Starting with the NOAEL dose you will need to back down by ten fold increments to the next three lower doses which you will then use for your "effective dose" response analyses. For example, if the NOAEL is 100 mg/kg, then your dose response analysis should start with 0.1mg/kg, then 1.0 mg/kg and then 10.0 mg/kg. This should give you a good baseline set of dose response data for therapeutic index which can then be translated to NHP and humans using allometric scaling. This is all designed for first estimates. If your investigational drug has a narrow therapeutic index you will need to determine if it came be modified structurally to improve safety while retaining efficacy.
I agree with Marcia H. Ratner, very good explanation and instruction.
Marcia H. Ratner
Thanks for your answer. We have tested the toxicity of this drug using various tests in vitro conditions such as MTT assay, fortunately, no significant toxicity was observed. As a complementary test, the effect of this drug on human red blood cell lysis was also tested that at very high doses, about 2% of lysis was observed, however, your comment was very helpful and practical in our study.
Thanks
Hi, If you are testing the new drug follow the dose response curve for effectiveness. Because your drug is not showing any toxicity now, then choose the median dose to start. If you are comparing with a known drug, then always use the conversion of the most prescribed dose for parkisonism.
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