Pharmacokinetics of traditional Chinese syndrome and recipe: a hypothesis and its verification (I).
AIM:To propose a hypothesis defining the absorption, distribution, metabolism and elimination of traditional Chinese recipe (TCR)component in blood of healthy subjects and patients, and estimate its correctness.METHODS:The pharmacokinetics (PK) of same dose of drug was studied in the animal model of traditional Chinese syndrome (S)and healthy animals. The classification, termi-nology, concept and significance of the hypothesis were set forth with evidence provided in the present study. The hypotheses consisted of traditional Chinese syndrome PK (S-PK) and traditional Chinese recipe PK (R-PK). Firstly, the observed tetramethylpyrazine (TMP) PK in healthy, chronically reserpinized rats (rat model of spleen deficiency syndrome, RMSDS) and RMSDS treated with Sijunzi decoction (SJZD) for confirmation were used to verify S-PK; secondly, the ferulic acid (FA) PK in healthy and high molecular weight dextran (HMWD)-induced rabbit model with blood stasis syndrome (RDBSS) was also used to verify S-PK; and lastly, TMP PK parameters in serum of healthy rats after orally taken Ligusticum wallichii (LW), LW and Salvia miltiorrhiza (LW&SM) decoctions were compared to verify R-PK.RESULTS:The apparent first-order absorption Ka,(13.61 plus minus 2.56)h(-1) ,area under the blood drug concentration-time curve AUC, (24.88 plus minus 9.76)&mgr;gcenter doth(-1)mL(-1) , maximum drug concentration C(max), (4.82 plus minus 1.23)&mgr;gcenter dotmL(-1) of serum TMP in RMSDS were increased markedly(P< 0.05) compared with those Ka = (5.41 plus minus1.91)h(-1), AUC = (5.20 plus minus 2.57)&mgr;gcenter doth(-1)center dotmL(-1), C(max) = (2.33 plus minus 1.77)&mgr;gcenter dotmL(-1) of healthy rats (HR). The apparent first-order rate constant for alpha and beta distribution phase alpha = (0.38 plus minus 0.09)h(-1), beta = (0.06 plus minus 0.03)h(-1) , the apparent first-order intercompartmental transfer rate constants K10 = (0.24 plus minus 0.07)h(-1), K(12) = (0.11 plus minus 0.02)h(-1), K(21) = (0.11 plus minus 0.02)h(-1) of serum TMP in RMSDS were decreased significantly (P <0.01) compared with those K(10) = (0.88 plus minus 0.20)h(-1), K(12) = (1.45 plus minus 0.47)h(-1), K(21) = (0.72 plus minus 0.22)h(-1) of HR. However, no apparent differences occurred between HR and RMSDS treated with SJZD. The serum FA concentration and its AUC (5.6690 plus minus 2.3541)&mgr;gcenter doth(-1)center dotmL(-1) in RMBSS were also higher than those AUC =(2.7566 plus minus0.8232)&mgr;gcenter doth(-1)center dotmL(-1) of healthy rabbits (P <0.05). The Ka (11.51 plus minus 2.82)h(-1), AUC (0.84 plus minus0.17)&mgr;gcenter doth(-1)center dotmL(-1) of LW & SM-derived TMP in serum were much lower (P <0.05) than those Ka = (19.58 plus minus 4.14)h(-1),AUC = (1.27 plus minus 0.26)&mgr;gcenter doth(-1)center dotmL(-1) of LW-derived TMP in serum after oral decoctions.CONCLUSION:The SDS and blood stasis syndrome state could affect significantly the pharmacokinetic parameters of drugs and the abnormal SDS pharmacokinetic parameters could be normalized by SJZD. The combination of Chinese medicine in TCR could reciprocally affect the pharmacokinetic parameters of other components absorbed into the systemic circulation. These results support the S and R-PK hypothesis.
Huang
Xi
X
Ren
Ping
P
Wen
Ai-Dong
AD
Wang
Li-Li
LL
Zhang
Li
L
Gao
Feng
F