Quinine hydrogen sulphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is not done according to OECD guideline, but it is a well documented study.

Data source

Reference

Reference Type:

publication

Title:

Effect of oral activated charcoal on quinine elimination.

Author:

Lockey, D. and Bateman, D. N.

Year:

1989

Bibliographic source:

Br. J. clin. Pharmac.27:92-94

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The protocol was approved by the local Ethics Committee and seven healthy male volunteers (mean age 21 years) agreed to participate in the experiment. On each of 2 days, separated by more than 1 week, the volunteers attended the clinical laboratory after an overnight fast. At 09:00 h a 600 mg dose of quinine bisulphate was given as tablets with 100 ml water. Blood samples were obtained before dosing with quinine, and subsequently at 3 h intervals for 15 h and at 24, 30 and 36 h. On one of the investigation days no additional treatment was given and subjects were allowed free access to food from 2 h after the dose of quinine. Plasma samples were separated by centrifugation and quinine was measured by a fluorimetric technique (Cramer & Isaksson, 1963) following organic extraction. Samples from each subject were analysed in the same batch, within assay coefficient or variation being less than 5% at 1 mg/L. The lower limit of detection was 0.05 mg/L.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Quinine hydrogen sulphate

EC Number:

208-970-9

EC Name:

Quinine hydrogen sulphate

Cas Number:

549-56-4

Molecular formula:

C20H24N2O2.H2O4S

IUPAC Name:

(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl](6-methoxyquinolin-4-yl)methanol; sulfuric acid

Test material form:

solid: pellets

Details on test material:

- Name of test material (as cited in study report): Quinine bisulphate

Radiolabelling:

no

Test animals

Species:

human

Sex:

male

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

600 mg dose of quinine bisulphate was given as tablets with 100 ml water.

Doses / concentrations

Remarks:

Doses / Concentrations:600 mg dose of quinine bisulphate

No. of animals per sex per dose / concentration:

seven healthy male volunteers (mean age 21 years)

Control animals:

not specified

Details on dosing and sampling:

At 09.00 h a 600 mg dose of quinine bisulphate was given as tablets with 100 ml water. Blood samples were obtained before dosing with quinine bisulphate, and subsequently at 3 h intervals for 15 h and at 24, 30 and 36 h. Plasma samples were separated by centrifugation and quinine was measured by a fluorimetric technique (Cramer & Isaksson, 1963) following organic extraction.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

AUC: 53.9 mg/L* h

Toxicokinetic parameters 2

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 8.23 h

Metabolite characterisation studies

Metabolites identified:

not specified

Any other information on results incl. tables

Pharmacokinetic parameters in subjects (n = 7) following 600 mg quinine bisulphate

Subject	t 1/2 (h)	AUC (mg/L * h)
1	8.25	38.4
2	8.67	35.2
3	6.40	56.9
4	11.09	62.1
5	8.13	52.6
6	8.17	59.9
7	6.93	72.0
Mean	8.23	53.9
s.e. mean	0.57	4.9

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study resultsThe AUC of quinine bisulphate was about 53.9 mg/L *h and the half-life in plasma is about 8.23 hours.

Executive summary:

In the study published by Lockey, 1989 the pharmacokinetic of quinine bisulphate was determined after oral ingestion. The AUC of quinine bisulphate is 53.9 mgl/L *h and the half-life in plasma is 8.23 hours.