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Basic toxicokinetics

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basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Except data obtained from the scientific literature, the studies performed either on Isosorbide (LAB 3085) or on LAB 3822 were performed according OECD good laboratory practices.
Reason / purpose for cross-reference:
reference to other study

Data source

Reference Type:
other: analysis by an expert
Analysis of pharmacokinetics available data for Isosorbide risk assessment
Report date:

Materials and methods

Results and discussion

Applicant's summary and conclusion

One application of isosorbide is the production of LAB 3822.
LAB 3822 contains then about 29 % of Isosorbide.
After administration, the LAB 3822 is hydrolysed by the pancreatic lipase. This hydrolysis split LAB 3822 into ISOSORBIDE and free fatty acids.
LAB 3822 is totally and rapidly transformed into isosorbide. Under these conditions, some of the toxicological studies were performed on LAB 3822 and data were extrapolated to isosorbide.

After administration of LAB 3822 (derivative of Isosorbide) animals are exposed to Isosorbide. The level of exposure is proportional to the dose. Exposure to isosorbide is higher when administered alone than when it is administered as LAB 3822, but the isosorbide dose equivalent administered at the maximum dose of LAB 3822 (0.67 g/kg) is largely lower that when it was administered alone (2g/kg). The T1/2 (plasma and urine) and Tmax (plasma) of isosorbide was not different when isosorbide is administered as LAB 3822 or as Isosorbide itself. In both cases males are more exposed than females. The excretion of isosorbide is almost in the urine as unchanged isosorbide.
The available data are sufficient to conclude that no pharmacokinetic study is needed for risk assessment.