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Aptivus®

Boehringer Ingelheim

Kapsel, mjuk 250 mg
(Tillhandahålls ej) (Rosafärgad kapsel märkt TPV 250)

Proteashämmare

Aktiv substans:
ATC-kod: J05AE09
Utbytbarhet: Ej utbytbar
Läkemedel från Boehringer Ingelheim omfattas av Läkemedelsförsäkringen.
  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan

Tipranavir

Miljörisk: Användning av tipranavir har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning: Tipranavir är potentiellt persistent.
Bioackumulering: Tipranavir har låg potential att bioackumuleras.


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Detaljerad miljöinformation

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 1.5 x 10-4 /5.0 = 3.0 x 10-5, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of Tipranavir has been considered to result in insignificant environmental risk.”


Predicted Environmental Concentration (PEC)

PEC (μg/L) = (A*109*(100-R))/ (365*P*V*D*100) = 1.5*10-6*A (100-R) = 1.5 x 10-4 µg/L


Where:

A is set to 1 kg for calculation purposes, as the current sold amount (year 2014, data from IMS Health) as well as the forecasted sales amount API in Sweden is 0 kg/year.

R = 0 % removal rate.

P = number of inhabitants in Sweden = 9 *106

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

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (I)


Predicted No Effect Concentration (PNEC)

PNEC =5.0 μg/L

The PNEC has been derived from the lowest EC50 (Daphnia magna, 48h) of 5.0 mg/L An assessment factor of 1000 is used based on the availability of acute toxicity studies for all trophic levels in accordance with ECHA Guidelines (I).


Algae (Green algae, Desmodesmus subspicatus) (OECD 201, GLP) (II):

EC50 96h (growth rate) = > 40.4 mg/L (solubility limit)

NOEC 96h (growth rate) = 40.4 mg/L (solubility limit)

EC50 96h (biomass) = > 40.4 mg/L (solubility limit)

NOEC 96h (biomass) = 40.4 mg/L (solubility limit)


Crustacean (Water flea, Daphnia magna) (OECD 202, GLP) (III):

Acute toxicity

EC50 48h = 5.0 mg/L

NOEC 48h = 3.96 mg/L


Fish (Rainbow trout, Oncorhynchus mykiss) (OECD 203, GLP) (IV):

Acute toxicity

LC50 96h = > 15.4 mg/L

NOEC 96h = 1.0 mg/L


Microorganisms (OECD 209, GLP) (V):

No influence on the respiration rate of activated sludge microorganisms was observed up to 1000 mg/L.


Degradation


Biotic degradation


Ready degradability:

Tipranavir was degraded 9% in 28 days in an OECD Guideline 301F study (GLP) (VI) and degraded 4% in 42 days in an US-FDA, TAD 3.11 Guideline study (VII).


Inherent degradability:

No data on inherent biodegradability.


Simulation studies:

No data on simulation studies.


Abiotic degradation

Hydrolysis: No data on hydrolysis

Photolysis: No data on photolysis.


Adsorption/Desorption

The adsorption coefficient log Koc of Tipranavir was determined to 2-2.7 in an OECD Guideline 121 (GLP) study (VIII).


Justification of chosen degradation phrase:

Tipranavir did not pass two separate ready degradation tests and data on abiotic degradation is lacking. Tipranavir did not show substantial potential for distribution to soil/sludge. Based on these data combined, Tipranavir is considered “potentially persistent”.


Bioaccumulation

Bioconcentration factor (BCF):

The bioconcentration factor of Tipranavir was determined to between 10-20 and 30-50 in an OECD Guideline 305 (GLP) study (IX).


Partitioning coefficient:

Tipranavir has a log Kow of 4.0 at pH 4.2 (OECD 117, GLP) (X).


Justification of chosen bioaccumulation phrase:

Based on the data from the OECD Guideline 305 study showing a BCF of 10-50 (IX), Tipranavir is considered to have “low potential for bioaccumulation”.


Excretion (metabolism)

A human 14C-ADME study on Tipranavir demonstrated that most of the radioactivity is excreted in feces with a small amount excreted in urine (XI). Less than 5 % of the administered dose was excreted in feces and urine as metabolites. The most abundant metabolites in feces are two mono-hydroxylated Tipranavir species. Due to the low levels of metabolites excreted under treatment conditions and in line with the respective guidance documents, there has not been a follow-up on metabolite structures e.g. for their potential environmental impact.


PBT/vPvB assessment

Tipranavir is considered not to fulfil the criteria for PBT or vPvB.


References

  1. European Chemicals Agency (ECHA). 2008 Guidance on information requirements and chemical safety assessment. Chapter R.10: Characterization of dose[concentration]-response for environment. http://echa.europa.eu/documents/10162/13632/information_requirements_r10_en.pdf

  2. Boehringer Ingelheim GmbH internal report U04-1377

  3. Boehringer Ingelheim GmbH internal report U04-1375

  4. Boehringer Ingelheim GmbH internal report U04-1367

  5. Boehringer Ingelheim GmbH internal report U04-1376

  6. Boehringer Ingelheim GmbH internal report U04-1373

  7. Boehringer Ingelheim GmbH internal report U04-0063

  8. Boehringer Ingelheim GmbH internal report U04-1576

  9. Boehringer Ingelheim GmbH internal report U04-0233

  10. Boehringer Ingelheim GmbH internal report U04-1374

  11. Boehringer Ingelheim ERA data sheet, 2005