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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1975
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only Summary but Basic data given

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Objective of study:
absorption
other: Pharmacokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Beagle dogs were dosed orally with a single dose of sodium valproate.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium valproate
EC Number:
213-961-8
EC Name:
Sodium valproate
Cas Number:
1069-66-5
Molecular formula:
C8H16O2.Na
IUPAC Name:
sodium 2-propylpentanoate
Details on test material:
- Name of test material (as cited in study report): Sodium Valproate
Radiolabelling:
not specified

Test animals

Species:
dog
Strain:
Beagle
Sex:
female

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: 0.05 M bicarbonate buffer pH 9 (400 mg/mi) or PEG400 (25mg/ml, 100mg/ml)
Doses / concentrations
Remarks:
Doses / Concentrations:
Oral: 25, 50, 100, 200mg/kg
No. of animals per sex per dose / concentration:
6
Control animals:
no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Oral doses are well absorbed, see AUC.
Toxicokinetic parametersopen allclose all
Test no.:
#1
Toxicokinetic parameters:
AUC: 99.9 ± 14.9mg.h/l (dose: 25mg/kg, time: 0-12h)
Test no.:
#2
Toxicokinetic parameters:
AUC: 240.5 ± 17.6mg.h/l (dose: 50mg/kg, time: 0-12h)
Test no.:
#3
Toxicokinetic parameters:
AUC: 820.0± 155mg.h/l (dose: 100mg/kg, time: 0-12h)
Test no.:
#4
Toxicokinetic parameters:
AUC: 1251.5 ± 168.9mg.h/l (n=3) (dose: 200mg/kg, time: 0-12h)
Test no.:
#5
Toxicokinetic parameters:
AUC: 1171.0 ± 36.9mg.h/l (n=3; dose: 200mg/kg, time: 0-12h; animals fed 7 hours post-dosing)

Metabolite characterisation studies

Metabolites identified:
not measured

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: See conclusions
Oral doses are well absorbed. Plasma concentration of valproate is proportional to dose. The pharmacokinetic in the beagle dog can not be described either by the one or two compartment open models. In animals who were fed at 7 hours, plasma concentrations were greater at 8 hours than 6 hours which could be the result of biliary secretion and reabsorption.