Amoxicillin

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Although the study was not conducted according to the recommended guidelines, it provides scientific valid information to assess the pharmacokinetics of the substance.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1972

Materials and methods

Objective of study:

absorption

excretion

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Eight healthy adult male volunteers received two 250-mg capsules of amoxicillin. The volunteers reported to the laboratory after an overnight fast and were instructed to empty their bladders. They were then given the antibiotic capsules with 100 ml of water, and were allowed no food during the first 3 hr of the experiment. Blood samples taken at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hr, and samples of urine collected between 0 to 4 and 4 to 8 hr.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amoxicillin

EC Number:

248-003-8

EC Name:

Amoxicillin

Cas Number:

26787-78-0

Molecular formula:

C16H19N3O5S

IUPAC Name:

6-{[amino(4-hydroxyphenyl)acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Details on test material:

- Name of test material (as cited in study report): Amoxicillin (BRL-2333, a-amino-p-hydroxybenzyl penicillin)

Radiolabelling:

no

Test animals

Species:

human

Sex:

male

Details on test animals or test system and environmental conditions:

- Fasting period before study: The volunteers reported to the laboratory after an overnight fast and were instructed to empty their bladders.

Administration / exposure

Route of administration:

oral: capsule

Vehicle:

unchanged (no vehicle)

Details on exposure:

Subjects were then given the antibiotic capsules with 100 mL of water, and were allowed no food during the first 3 hr of the experiment.

Duration and frequency of treatment / exposure:

Single dose

Doses / concentrations

Remarks:

Doses / Concentrations:
500 mg of amoxicillin

No. of animals per sex per dose / concentration:

8 men

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, blood, serum
- Time and frequency of sampling: Blood samples taken at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hr, and samples of urine collected between 0 to 4 and 4 to 8 h.

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

mean peak serum concentration of 7.6 µg/mL

Main ADME results 2

Type:

excretion

Results:

The average 8-hr urinary excretion of amoxicillin was 60.2% of the dose administered.

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters 1

Toxicokinetic parameters:

Cmax: 7.61 µg/mL

Toxicokinetic parameters 2

Toxicokinetic parameters:

Tmax: 1.5 h

Toxicokinetic parameters 3

Toxicokinetic parameters:

half-life 1st: 61.3 (±5.6) min

Applicant's summary and conclusion

Conclusions:

The absorption of amoxicillin was demonstrated by a mean peak serum concentration of 7.61 µg/ml (maximum occurred at 1.5 hours).

Executive summary:

Amoxicillin (α-amino-p-hydroxybenzyl penicillin) was administered orally in 500-mg doses to eight fasting volunteers in which pharmacokinetic techniques were used. The absorption of amoxicillin was demonstrated by a mean peak serum concentration of 7.61 µg/ml (maximum occurred at 1.5 hours). At 8 hr, all of the volunteers had measurable levels of test substance (>0.1 µg/ml). Serum half-lives derived from these regression lines averaged 61.3 (±5.6) min for test substance. The average 8-hr urinary excretion of amoxicillin was 60.2% of the dose administered.