Mycophenolic acid

Detailed information

Mycophenolate mofetil and sodium mycophenolate

According to the Fass for Cellcept (mycophenolic acid): After oral administration, mycophenolate mofetil is rapidly and completely absorbed. Presystemically, mycophenolate mofetil is completely metabolized to the active metabolite, MPA. MPA = mycophenolic acid. MPA is mainly metabolized by glucuronyl transferase (isoform UGT1A9) to the inactive phenol glucuronide of MPA (MPAG). […] Most (about 87%) of the administered dose was excreted in urine as MPAG. Glucuronide conjugates can be split off in waste water treatment plants and generate active substance again (Larsson et al, 1999). Sodium mycophenolate dissociates in an aqueous phase to mycophenolic acid. The interesting substance from an environmental point of view should be mycophenolic acid.

Comment on Fass environmental information

Mycophenolic acid has different classifications on fass.se. According to Lif (the trade association for the research-based pharmaceutical industry in Sweden) the various pharmaceutical companies compile environmental information for their active substances based on internal studies and published data. Based on data, which may thus differ between different pharmaceutical companies, the companies assess the environmental risk with guidance from “Environmental classification of pharmaceuticals at www.fass.se – Guidance for pharmaceutical companies 2012”. The Swedish Environmental Institute (IVL) reviews the assessment but does not have the task of coordinating/harmonizing environmental information from different pharmaceutical companies for the same active substance.

Fass environmental information for Myfortic

Fass environmental information for Myfortic from Novartis (mycophenolic acid) (downloaded 2023-09-19).

Hazard

Persistence: "2.0–5.0 % degradation in 28 days, not readily biodegradable (OECD301)."

Bioaccumulation: Log P: 1.6 (method unknown, no reference available).

Chronic toxicity: There are data for 3 trophic levels, lowest for fish (zebrafish; Danio rerio) 1.32 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2021. PEC/PNEC = 2.99 ~ 3.0 which gives the risk moderate.

Fass environmental information for Cellcept

Fass environmental information for Cellcept from Roche (mycophenolic acid) (downloaded 2023-09-19).

Hazard

Persistence: Mycophenolate mofetil/Mycophenolic acid is not readily degradable. In sediment/water fate systems significant removal (up to >50%) of radio-labelled MPA was noted after 64 days. There is additional evidence for some aquatic photodegradation. In a biodegradation test in activated sludge according to OECD 314B a mineralisation of 82% was observed within 28 days. This justifies the phrase 'Mycophenolate mofetil/Mycophenolic acid is slowly degraded in the environment.'

Bioaccumulation: Log D_ow = 2.28 (pH 5, 25 °C) (OECD 107)
= 0.47-0.48 (pH 7, 25 °C) (OECD 107)
= -1.83 - -1.54 (pH 9, 25 °C) (OECD 107)
Mycophenolate mofetil/Mycophenolic acid has low potential for bioaccumulation (log K_OW < 4).

Chronic toxicity: There are data for 3 trophic levels, lowest for fish (zebrafish; Danio rerio) 5.8 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2021. PEC/PNEC = 0.6 which gives the risk low.

Assessment report

Assessment report for Myclausen (mycophenolate mofetil), EMA/CHMP/451012/2010.

"An Environmental Risk Assessment has been submitted by the applicant. Myclausen is a generic product, which is deemed interchangeable with already marketed products, and is unlikely to increase the combined sales volumes of mycophenolate mofetil-containing products thus not having an adverse effect on the environment."