N-amidinosarcosine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

01/1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Materials and methods

Objective of study:

other: bioavailability

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The difference in absorption of creatine citrate and creatine monohydrate was elucidated. The impact on bioavailability was tested by administering 5 g of the two substances, corresponding to 4.4 g creatine as creatine monohydrate and 2.0 g of creatine as creatine citrate. The study was conducted according to the experimental design as a controlled, crossover, following a Latin-Square design with randomised sequences and a 7-day wash-out between the two administrations in 10 healthy volunteers.

GLP compliance:

no

Remarks:

Principals for Good Clinical Practices

Test material

Test material information

Constituent 1

Reference substance name:

N-(aminoiminomethyl)-N-methyl-Glycine, monohydrate

Cas Number:

6020-87-7

Molecular formula:

C4H9N3O2*H2O

IUPAC Name:

N-(aminoiminomethyl)-N-methyl-Glycine, monohydrate

Details on test material:

- Name of test material (as cited in study report): Creatine Monohydrate
- Lot/batch No.: 970068
- Expiration date of the lot/batch: 07/00

Radiolabelling:

no

Test animals

Species:

other: Human

Details on species / strain selection:

Ten subjects, healthy volunteers, responding to the admission and
exclusion criteria below reported were admitted to the study.
The admission criteria were the following:
• Adults, both sexes, aged between 18 and 55 years ;
• Written informed consent.
• Normal vital signs.
• Subjects with normal liver and kidney function on the basis of
medical history, physical exam and biological tests (results within
a clinically acceptable normal range as judged by the responsible
physician).
• Body mass no more than 20% above or below the normal weight
for height and age.
• Absence of concomitant treatments
• co-operative subjects able to comply with the planned procedure.

The exclusion criteria were the following:
• Unable to give informed consent.
• History of hypersensitivity to the study drug or any related drugs.
, History of abuse or dependence to alcohol or drugs in the last 2
years, chronic use of barbiturics in the 30 days preceding the
study.
• Abnormal renal function evaluated in terms of BUN and
Creatinine.
• Abnormal hepatic function evaluated in terms of total Bilirubin,
transaminases, and y-GT
• Concomitant participation in another study within the month
preceding the study. ·
• Female at risk of pregnancy who are sexually active and not using
any reliable method of contraception (estroprogestative
anticonceptive treatment is not accepted).

Sex:

male/female

Administration / exposure

Route of administration:

other: oral formulation

Vehicle:

not specified

Details on exposure:

the treatment scheduled in the morning of the test day after an overnight fast ; second treatment after one-week wash-out

Duration and frequency of treatment / exposure:

single oral dose

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

5 other: g

Remarks:

5 g Creatine Monohydrate correspording to 4.4 g creatine

Doses / concentrations 2

Dose / conc.:

5 other: g

Remarks:

5 g Creatine Citrate correspording to 2.0 g creatine

No. of animals per sex per dose / concentration:

7 males and 3 females

Control animals:

no

not specified

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood, plasma, (urine was only sampled after the overnight fasting before the treatment)
- Time and frequency of sampling: plasma sampling: just before (timepoint o), 0.5, 1, 2, 3, 4, 5, 6 and 8 hours after treatment


METABOLITE CHARACTERISATION STUDIES
- the Creatine plasma determination was performed by using a specific, sensitive and validated method (method is detailled in analytical report which was not available)

Statistics:

The variation between subjects was assumed to be random and the sequence effect was tested using the between subject (within sequence) mean square in the analysis of variance (ANOVA). The error variance obtained from ANOVA was used to construct the 90% confidence interval for the ratio of the test drug versus the reference drug.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Creatine citrate more rapidly absorbed, confirming the greater observed solubility in vitro.

Details on distribution in tissues:

no data

Details on excretion:

no data

Toxicokinetic parameters

Toxicokinetic parameters 1

Key result

Test no.:

#1

Toxicokinetic parameters:

AUC: 310.1 +/- 41.4 µg/ml*h

Toxicokinetic parameters 2

Key result

Test no.:

#2

Toxicokinetic parameters:

Cmax: 2.1 +/- µg/ml

Toxicokinetic parameters 3

Key result

Test no.:

#3

Toxicokinetic parameters:

Tmax: 2.4+/-0.2 h

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

no data

Applicant's summary and conclusion

Conclusions:

no bioaccumulation potential based on study results
The relative bioavailability of the citrate versus the monohydrate form is equivalent to 0.97+/-0.11.

Executive summary:

The relative bioavailability of creatine citrate versus creatine monohydrate is equivalent to 0.97, thus indicating an analogaus absorption for the two preparations.

The time to reach the peak of concentration is anticipated for creatine citrate. Creatine citrate is more rapidly absorbed, confirming the greater observed solubility in vitro.

No adverse reactions were reported with the two formulations.