Detaljerad miljöinformation

Detailed background information

Midodrine is the pro-drug of desglymidodrine. The conversion of midodrine hydrochloride to desglymidodrine is rapid with peak plasma concentrations in humans within an hour of an oral dose (Ref. 1). The environmental risk assessment is for midodrine and the active moiety desglymidodrine.

Environmental Risk Classification

Predicted Environmental Concentrations (PECs)

PECs are calculated according to the following formula:

PEC (μg/L) = (A*10⁹*(100-R))/(365*P*V*D*100) = 1.37*10^-6*A(100-R)

Where:

R = 0 % removal rate.

P = number of inhabitants in Sweden = 10*10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref. 2)

D = factor for dilution of wastewater by surface water flow = 10 (ECHA default) (Ref. 2)

A (midodrine hydrochloride, molecular weight = 290.74 g/mol) = 5.9356 kg. (Data for the total amount of midodrine hydrochloride sold in Sweden year 2022 from IQVIA).

PEC (midodrine hydrochloride) = 0.000814 μg/L

A (desglymidodrine, molecular weight = 197.23 g/mol) = 4.0265 kg

PEC (desglymidodrine) = 0.000552 μg/L

According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of midodrine hydrochloride is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) at the time of registration was below the action limit 0.01 µg/L.

Predicted No Effect Concentration (PNEC)

No ecotoxicological data are available for midodrine and desglymidodrine.

Environmental risk classification (PEC/PNEC ratio)

As no ecotoxicological data are available, the PEC/PNEC ratio cannot be calculated. This justifies the phrase "Risk of environmental impact of midodrine hydrochloride/ desglymidodrine cannot be excluded, since no ecotoxicity data are available".

Degradation

No degradation data are available for midodrine and desglymidodrine.

Bioaccumulation

Partitioning coefficient:

Log K_ow (midodrine) = 0.28 (OECD 107) (Ref. 3, 4)

Log K_ow (desglymidodrine) = -0.49, -0.95 (calculated) (Ref. 5)

Since log K_ow < 4, midodrine and desglymidodrine have low potential for bioaccumulation.

References

1. Australian Prescriber (2021). Midodrine for orthostatic hypotension 44, 31. https://doi:10.18773/austprescr2020.081

2. ECHA (2008). Guidance on information requirements and chemical safety assessment. European Chemicals Agency. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm

3. Desglymidodrine Partition Coefficient (2015). Huntingdon Life Sciences. HLS study number TCD0001.

4. Taylor, J. R. (2020). Environmental Risk Assessment for Bramox (midodrine hydrochloride). ProPhase Development Ltd on behalf of Brancaster Pharma Limited.

5. PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/18340