Published online Jun 15, 2000. doi: 10.3748/wjg.v6.i3.384
Revised: January 13, 2000
Accepted: January 22, 2000
Published online: June 15, 2000
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, terminology, concept and significance of the hypothesis we re set forth with evidence provided in the present study. The hypotheses consist ed of traditional Chinese syndrome PK (S-PK) and traditional Chinese recipe PK (R-PK). Firstly, the observed tetramethylpyrazine (TMP) PK in healthy, chronica lly reserpinized rats (rat model of spleen deficiency syndrome, RMSDS) and RMSDS treated with Sijunzi decoction (SJZD) for confirmation were used to verify S-P K; 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 (LWandS M) decoctions were compared to verify R-PK.
RESULTS: The apparent first-order absorption [Ka, (13.61 ± 2.56) h-1], area under the blood drug concentration-time curve [AUC, (24.88 ± 9.76) μg·h-1·mL-1], maximum drug concentration [Cmax, (4.82 ± 1.23) μg·mL-1] of serum TMP in RMSDS were increased markedly (P < 0.05) compared with those [Ka = (5.41 ± 1.91) h-1, AUC = (5.20 ± 2.57) μg·h-1·mL-1, Cmax = (2.33 ± 1.77) μg·mL-1] of healthy rats (HR). The apparent first-order rate constant for α and β distribution phase [α = (0.38 ± 0.09) h-1, β = (0.06 ± 0.03) h-1], the apparent first-order intercom partmental transfer rate constants [K10 = (0.24 ± 0.07) h-1, K12 = (0.11 ± 0.02) h-1, K21 = (0.11 ± 0.02) h-1] of serum TMP in RMSDS were decreased significantly (P < 0.01) compared with those [K10 = (0.88 ± 0.20) h-1, K12 = (1.45 ± 0.47) h-1, K21 = (0.72 ± 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 ± 2.3541) μg·h-1·mL-1] in RMBSS were also higher than those [AUC = (2.7566 ± 0.8232) μg·h-1·mL-1] of healthy rabbits (P < 0.05). The Ka (11.51 ± 2.82) h-1, AUC (0.84 ± 0.17) μg·h-1·mL-1 of LW and SM-derived TMP in serum were much lower (P < 0.05) than those [Ka = (19.58 ± 4.14) h-1, AUC = (1.27 ± 0.26) μg·h-1·mL-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.