Caffeine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Review, comparable with reliability 2, data from Handbook or collection of data, selected for ICCA RSS.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

No information

Author:

Arnaud MJ et al.

Year:

1988

Bibliographic source:

In: Proc Third Int Symp, Innsbruck, Austria, 17-21 July 1988. Edited by Baille TA and Jones JR; pp. 645-648.

Reference 2

Reference Type:

publication

Title:

No information

Author:

Arnaud MJ

Year:

1993

Bibliographic source:

In: Caffeine, Coffee and Health. Edited by Garattini S. Raven Press, New York; pp. 43-95.

Reference 3

Reference Type:

review article or handbook

Title:

No information

Author:

IARC

Year:

1991

Bibliographic source:

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 51, International Agency for Research on Cancer, Lyon, France; pp. 291-390.

Reference 4

Reference Type:

publication

Title:

No information

Author:

Nau H

Year:

1987

Bibliographic source:

In: Pharmacokinetics in Teratogenesis Vol. 1. Edited by Nau H and Scott WJ. CRC Press, Boca Raton, Florida; pp. 81-106.

Reference 5

Reference Type:

review article or handbook

Title:

No information

Author:

Sawynok and Yaksh TL

Year:

1993

Bibliographic source:

Pharmacol Rev 45: 43-85.

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

no data

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Caffeine

EC Number:

200-362-1

EC Name:

Caffeine

Cas Number:

58-08-2

Molecular formula:

C8H10N4O2

IUPAC Name:

1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione

Details on test material:

caffeine
no further data

Results and discussion

Any other information on results incl. tables

Data on absorption, distribution, metabolism and excretion in experimental animals were summarized.

• Caffeine absorption and distribution from gastrointestinal tract is rapid and complete and it is distributed to all body fluids and appeared in all tissues within 5 min.
• There is no accumulation of caffeine or its metabolites in any organ even after high doses.
• No blood-brain barrier or placental barrier was detected.
• The fraction bound to plasma albumin varies from 10 to 30%.
• It is eliminated by various species by first-order kinetics, described by a one-compartment open model system.
• The half-life for several species ranged between 0.7 to 12 h (rats to baboons) and a mean volume of distribution of 0.8 l/kg has been reported for various species. Decreased as well as increased half-lives were found in pregnant animals.
• Caffeine is metabolized by liver microsomal mixed-function oxidases and can increase metabolizing enzymes at high doses (75 mg/kg).
• Caffeine is eliminated in animals by biotransformation to dimethylxanthines, dimethyl- and monomethyluric acids and uracil derivatives. Differences in formation and elimination of metabolites were noted in rats, mice and Chinese hamsters and mainly in monkeys, where it is almost completely metabolized to theophylline. In contrast, the acetylated uracil derivative, 5-acetylamino-6-formylamino-3-methyluracil, one of the most important metabolites in human, was not found in rodents or other species.
• Pharmacokinetic differences were recognized in mice after oral administration, which may account for interstrain variation in toxicity and in rabbits two subpopulations were described with slow or rapid metabolizing capacity.

Data from IARC (1991).
For further reviews see Nau (1987); Arnaud (1993); Arnaud et al.(1988); Sawynok and Yaksh (1993).