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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
mechanistic studies
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no details of the volunteers in test and no details on the test product used

Data source

Reference
Reference Type:
publication
Title:
Note: Determination of low concentrations of dibenzylamine in human plasma and urine by gas chromatography with a nitrogen-phosphorus detector
Author:
Calvo MB, Pedraz JL, Domínguez-Gil
Year:
1989
Bibliographic source:
J Chromat 490, 206-212

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
3 volunteers received single intramuscular injection of the Cefazolin-dibenzylamin complex and plasma content and urinary excretion of dibenzylamin was determined chromatographically
GLP compliance:
no
Type of method:
in vivo
Endpoint addressed:
basic toxicokinetics

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
cephazoline-dibenzylamine complex

Test animals

Species:
human
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
volunteers were injected i.m. the test substance

Administration / exposure

Route of administration:
intramuscular
Vehicle:
not specified
Details on exposure:
Single i.m injection of the complex into 3 voluteers
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
single application
Frequency of treatment:
single application
Post exposure period:
determination of debenzylamine in plasma and urine in intervalls up to 36 hours post treatment (further details not given)
Doses / concentrations
Remarks:
Doses / Concentrations:
1250 mg/person
Basis:

No. of animals per sex per dose:
3 volunteers
Control animals:
no
Details on study design:
3 volunteers received single intramuscular injection of the Cefazolin-dibenzylamin complex and plasma content and urinary excretion of dibenzylamine was determined chromatographically

Examinations

Examinations:
determination of dibenzylamine in blood (plasma) and urine
Positive control:
no

Results and discussion

Details on results:
Pharmacokinetic parameters of dibenzylamine in healthy volunteers after intramuscular injections of Cephazoline-dibenzylamine complex (mean vlues)
observation time: 36 hours
The absorption rate constant .33 per hour
The half-life of dibenzylamine: 6.33 hours
t(max): 5.23 hours
C( max): 1412.6 ng/ml
Area Under the Curve (AUC): 2296..5 ng h/ml
urinary excretion: 6.73 %

According to these findings and using the normal dosage interval of 24 h, the degree of accumulation of dibenzylamine between the first dose and the steady state would be 1.07

Applicant's summary and conclusion

Executive summary:

Pharmacokinetics of dibenzylamine was investigated by an intramuscular injection of 1250 mg of a cefazoline-dibenzylamine-complex into 3 volunteers.Blood and urine content was measured chromatographically in time intervals up to at least 36 hours.The following determinations were made: absorption rate constant .33 per hour; half-life of dibenzylamine: 6.33 hours; t(max): 5.23 hours;

C( max): 141.6 ng/ml; Area Under the Curve (AUC): 2296.5 ng h/ml; urinary excretion: 6.73 %

According to these findings and using the normal dosage interval of 24 h, the degree of accumulation of dibenzylamine between the first dose and the steady state would be 1.07 (Calvo 1989)