Simplified approach for evaluation of hepatic drug-oxidizing capacity with a simultaneous measurement of caffeine and its primary demethylated metabolites in carbon tetrachloride-intoxicated rats

E. Tanaka Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan

A. Ishikawa Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan

Y. Yamamoto Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan

E. Uchida Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan

S. Kobayashi Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan

H. Yasuhara Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan

S. Misawa Institute of Clinical Medicine, University of Tsukuba, Ibaraki-ken, Japan

show all

Abstract

1. Prediction of hepatic injury from changes in blood concentrations of caffeine (CA) and its three primary metabolites (theobromine: TB; paraxanthine: PX; theophylline; TP) after CA administration has been studied in carbon tetrachloride (CCl₄)-intoxicated rats.

2. The plasma half-life (t_1/2) of CA (10mg/kg, oral) was increased, and total body clearance (CL) decreased, in CCl₄-treated rats; the apparent volume of distribution (V_d) was relatively unchanged.

3. The ratios of CA to the three metabolites (TB/CA, PX/CA, TP/CA) were significantly decreased compared to those of controls.

4. There were good correlations between the ratios of TB/CA, PX/CA, and TP/CA and CL of CA(TB/CA; r = 0·944 at 1 h, r = 0·942 at 2 h: PX/CA; r = 0·974 at 1 h, r = 0·923 at 2 h: TP/CA; r = 0·866 at 1 h, r = 0·962 at 2 h).

5. Results indicate that it is possible to evaluate hepatic drug-oxidizing capacity by measuring the ratio of CA to its metabolites, using single blood sampling 1 or 2 h after CA administration in CCl₄-intoxicated rats.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Simplified approach for evaluation of hepatic drug-oxidizing capacity with a simultaneous measurement of caffeine and its primary demethylated metabolites in carbon tetrachloride-intoxicated rats

Information for

Open access

Opportunities

Help and information

Simplified approach for evaluation of hepatic drug-oxidizing capacity with a simultaneous measurement of caffeine and its primary demethylated metabolites in carbon tetrachloride-intoxicated rats

Abstract

Reprints and Corporate Permissions

Academic Permissions

Related research

To cite this article:

Download citation

Information for

Open access

Opportunities

Help and information

Keep up to date

Your download is now in progress and you may close this window

Login or register to access this feature