[The effect of tetramethylpyrazine on the pharmacokinetics of intragastrically administered cyclosporine A in rats].
OBJECTIVE
To investigate the possible effect of tetramethylpyrazine (TMP), an active ingredient of a commonly used Chinese herb, on the pharmacokinetics of cyclosporine A (CsA) by intragastric administration in rats.


METHODS
Forty male Sprague-Dawley rats were equally divided into four groups by randomized block design according to weight. On the first day, after each fasting rat was intragastrically administered CsA (10 mg x kg(-1)), blood samples (0.2 - 0.25 mL) were collected from the tail vein at 0, 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h. From day 4 to day 8, each group began to undergo different pretreatments with intragastric administration of water, verapamil (Ver), low and high dose TMP, separately. On day 9, each group intragastrically co-administered CsA (10 mg x kg(-1)) and different pretreatment compounds mentioned above, then blood samples were collected according to the schedule of the first day. The whole blood concentration of CsA was determined by HPLC. Main pharmacokinetic parameters were calculated and compared by statistic analysis.


RESULTS
In the group of water pretreated and co-administrated with CsA, no significantly different pharmacokinetic parameters of CsA were found. After Ver pretreatment and co-administration with CsA, AUC(0-48 h) and C(max) were increased significantly (P < 0.01 and P < 0.05); T(1/2) beta and CL were markedly prolonged and decreased (P < 0.05); T(max) and V were not apparently influenced. After low dose TMP pretreatment and co-administration with CsA, there was no significant difference in the pharmacokinetic parameters of CsA, in spite of the increasing trends of AUC(0-48 h) and C(max). After high dose TMP pretreatment and co-administration with CsA, AUC(0-48 h) and C(max) of CsA were increased significantly (P < 0.01), but there was no significant change in other parameters.


CONCLUSIONS
It was indicated that the high dose of TMP could apparently increase the intragastric absorption extent of CsA, while almost had no effect on its elimination process.
Liu
Xiao-lei
XL
Department of Clinical Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
Tang
Jing
J
Song
Juan
J
He
Juan
J
Xu
Ping
P
Peng
Wen-xing
WX
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D030004:Ligusticum / Q000737:chemistry; D008297:Male; D010946:Plants, Medicinal / Q000737:chemistry; D011719:Pyrazines / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D011719:Pyrazines; D016572:Cyclosporine; D014700:Verapamil; C017953:tetramethylpyrazine