Barbital sodium

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1961

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

unsuitable test system

Data source

Reference

Reference Type:

publication

Title:

Effect of temperature on toxicity and distribution of pentobarbital and barbital in rats and dogs.

Author:

SETNIKAR I, TEMELCOU O.

Year:

1961

Bibliographic source:

Journal of Pharmacology and Experimental Therapeutics. Vol. 135, Pg. 213, 1962.

Materials and methods

Objective of study:

other: blood level

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Remarks:

pre-GLP

Test material

Test material information

Constituent 1

Reference substance name:

Barbital sodium

EC Number:

205-613-9

EC Name:

Barbital sodium

Cas Number:

144-02-5

Molecular formula:

C8H11N2O3.Na

IUPAC Name:

sodium 5,5-diethyl-4,6-dioxo-1,4,5,6-tetrahydropyrimidin-2-olate

Test material form:

not specified

Test animals

Species:

dog

Strain:

other: Mongrel

Sex:

male

Details on test animals or test system and environmental conditions:

Male mongrel dogs, with a body weight of 6 to 15 kg, were used. Each dog was subjected to two experiments with a 7-day interval between them. In one, 12 hours before and after the injection of the barbiturate, the animal was kept at a room temperature of 15 ±1°C, in the other the dog was kept at 30 ± 1°C. This order was alternated so that half the dogs underwent the experiments in the cold environment first and half underwent the experiment in the warm environment first.

Administration / exposure

Route of administration:

intravenous

Vehicle:

not specified

Details on exposure:

Male mongrel dogs, with a body weight of 6 to 15 kg, were injected intravenously with the barbiturates. Each dog was subjected to two experiments with a 7-day interval between them. In one, 12 hours before and after the injection of the barbiturate, the animal was kept at a room temperature of 15 ±1°C, in the other the dog was kept at 30 ± 1°C. This order was alternated so that half the dogs underwent the experiments in the cold environment first and half underwent the experiment in the warm environment first. Averages of the barbital sodium blood levels observed at 10/20/30/40/60/90/120/180/240/300 minutes in six dogs kept at 30°C and at 15°C room temperature after an intravenous injection of 150 mg/kg of the drug were obtained.

Doses / concentrations

Dose / conc.:

150 other: mg/kg bw

No. of animals per sex per dose / concentration:

6 dogs per group

Details on dosing and sampling:

Averages of the barbital sodium blood levels observed at 10/20/30/40/60/90/120/180/240/300 minutes in six dogs kept at 30°C and at 15°C room temperature after an intravenous injection of 150 mg/kg of the drug were obtained. The barbital in the blood was determined by the method of Goldbaum (1948)as modified by Broughton (1956).

Statistics:

The straight-lines were calculated by the least squares method on the basis of the barbital blood levels observed from the 20th minute onwards. By analysis of the variance, the variance within the animals was separated and only this was considered for calculating the standard error of the slope function and of the straight-line constant.

Results and discussion

Main ADME results

Main ADME results 1

Type:

other: blood level

Results:

log mg/I = (2.332 ±0.003) - (2.212 ± 0.348)* 10^-4min (at 15°C room temperature)

Main ADME results 2

Type:

other: blood level

Results:

log mg/I = (2.331 ±0.003) - (3.254 ± 0.285)* 10^-4min (at 30°C room temperature)

Any other information on results incl. tables

Barbital sodium blood levels: No significant difference was found at the two temperatures for the slope functions or for the intersection point with the time = 0 ordinate (2.331 ± 0.004 at 15°C room temperature and 2.332 ± 0.005 at 30°C).

Applicant's summary and conclusion

Executive summary:

The barbital sodium blood levels observed in six dogs kept at 30°C and at 15°C room temperature after an intravenous injection of 150 mg/kg of the drug were determined.

Male mongrel dogs, with a body weight of 6 to 15 kg, were injected intravenously with the barbiturates. Each dog was subjected to two experiments with a 7-day interval between them. In one, 12 hours before and after the injection of the barbiturate, the animal was kept at a room temperature of 15 ± 1°C, in the other the dog was kept at 30 ± 1°C. This order was alternated so that half the dogs underwent the experiments in the cold environment first and half underwent the experiment in the warm environment first.

Two straight lines were calculated by the least squares method on the basis of the barbital blood levels observed from the 20th minute onwards: log mg/I = (2.332 ±0.003) - (2.212 ± 0.348)* 10^-4min  (at 15°C room temperature), log mg/I = (2.331 ±0.003) - (3.254 ± 0.285)* 10^-4min  (at 30°C room temperature).