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OBJECTIVE： To study the effects of Wuzhi soft capsule and imatinib mesylate tablet on the pharmacokinetics of imatinib in rats. METHODS： The rats were divided into single administration group and consecutive administration group. The single administration group was divided into imatinib group one （ig administration of blank soybean oil+imatinib suspension 10 mg/kg）， low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group （ig administration of Wuzhi soft capsule solution 134， 268， 536 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given imatinib suspension intragastrically 30 min after intragastric administration of blank soybean oil/Wuzhi soft capsule solution. The consecutive administration group was divided into imatinib group two （ig administration of blank soybean oil+imatinib suspension 10 mg/kg）， Wuzhi soft capsule low-dose+imatinib group （ig administration of Wuzhi soft capsule solution 134 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given blank soybean oil/Wuzhi soft capsule solution intragastrically for consecutive 14 d， once a day； 30 min after last administration， ig imatinib suspension. About 100 μL blood was collected before imatinib， 0.5， 1， 2， 2.5， 3， 4， 5， 6， 8， 12， 24 and 36 h after medication. The plasma concentration of imatinib was determined by HPLC-MS/MS. The pharmacokinetic parameters were fitted by using DAS 2.0 software. RESULTS： After single administration， compared with imatinib group one， cmax， t1/2， AUC0-36 h and AUMC0-36 h in low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group were increased significantly （P＜0.05 or P＜0.01）. After consecutive administration， compared with imatinib group two， cmax， t1/2 and AUMC0-36 h of imatinib+low-dose of Wuzhi soft capsule group were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Single administration and consecutive administration of Wuzhi soft capsule influence the pharmacokinetics of imatinib， increase plasma concentration of imatinib and prolong half-time.
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OBJECTIVE:To study the pharmacokinetic characteristics of Recombinant hirudin enteric-coated capsule by single and multiple administration in Beagle dogs. METHODS:12 Beagle dogs were divided into single ig group and single iv group by random control method,6 in each group. Recombinant hirudin 0.2 mg/kg was intragastrically administrated or intravenously inject-ed,blood sample was collected;after 2 weeks of cleaning,12 dogs were intragastrically administrated recombinant hirudin 0.2 mg/kg,for 7 d. Sample blood was collected,referred to multiple ig group. Recombinant hirudin concentration in plasma was deter-mined by enzyme-linked immunosorbent assay,and pharmacokinetic parameters were calculated by DAS 2.0 software. RESULTS:The results showed that pharmacokinetics by ig and iv recombinant hirudin in Beagle dogs fitted to two-compartment model,abso-lute bioavailability of ig Recombinant hirudin enteric-coated capsule was(14.908±1.868)%;the pharmacokinetic parameters in sin-gle ig group and multiple ig group were tpeak of(2.105±0.243),(3.000±0.000)h,t1/2β of(8.660±2.965),(14.870±2.710)h, cmax of(10.700±0.872),(12.05±1.587)ng/mL,AUC0-1440 min of(55.250±4.386),(58.978±6.002)ng·h/mL,without statistical significances in two groups(P>0.05). CONCLUSIONS:The ig Recombinant hirudin enteric-coated capsule can be absorbed into the blood to a certain extent. There is no accumulation for ig Recombinant hirudin enteric-coated capsule for several days,and it dose not change the pharmacokinetic characteristics.
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Aim To develop a HPLC method for the determination of the concentration of 1,8-TMP rhein in rat plasma and study the pharmacokinetics of 1,8-TMP rhein in rat plasma after single dose i. v. administration of 1,8-TMP rhein (2, 4, 8 mg·kg - 1 ). Methods Emodin was used as an internal standard. Plasma sam-ples were extracted with methanol and analyzed by HPLC. The mobile phase was methanol - 0. 1% for-mic acid water (78 ∶ 22, V/ V), with a flow rate of 1. 0 mL·min - 1 and UV 275 nm as the detection wave-length. The plasma concentration of 1,8-TMP rhein in rats was determined by HPLC after single-dose intrave-nous injection in rats with 2,4 and 8 mg·kg - 1 of 1,8-TMP rhein, and the pharmacokinetic parameters were caclulated by DAS 2. 1. Results The result of cali-bration curve was linear over the range of 0. 05 ~ 10. 00 mg·L - 1 (r = 0. 996 2). The lower limit of quantifica-tion was 0. 05 mg · L - 1 . The intra-day and inter-day precision (RSD% ) were both lower than 6% , and the extraction recoveries were higher than 88% , respec-tively. The validated method was successfully applied to a pharmacokinetic study after i. v. administration of 1,8-TMP rhein in rats with a dose of 2,4 and 8 mg· kg - 1 . The T1 / 2 was (68. 35 ± 1. 36), (69. 32 ± 2. 1) and (69. 32 ± 2. 03) min, respectively. The AUC0 - t was ( 101. 03 ± 24. 90 ), ( 144. 79 ± 3. 29 ) and (231. 92 ± 19. 30 ) min · mg · L - 1 , respectively. Conclusion A simple and specific HPLC method for the analysis of 1,8-TMP rhein is successfully developed and applied to a pharmacokinetic study in rat plasma.
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Aims To establish a UPLC-MS/MS meth-od for the determination of plasma concentration of scutellarein and its metabolite and to study their phar-macokinetics in rat plasma. Methods The analysis was achieved by BEH C18 column with a mobile phase composed of 0 . 1 % formic acid in acetonitrile and 0 . 1% aqueous formic acid using step gradient elution. A TQD tandem mass spectrometry equipped with electros-pray ionization source was used as detector and opera-ted by multiple reaction monitoring( MRM) positive ion mode. After intravenous injection of scutellarein, the concentrations of scutellarein and its major metabolite glucuronide scutellarin in rat plasma were determined at different time points. The pharmacokinetic parame-ters were calculated by DAS 2. 0 software. Results Good linearity was achieved for scutellarein, the ex-traction recovery was between 80 . 5 % to 90 . 5 %, the precisions and accuracy were good. The result showed the pharmacokinetic profiles of scutellarein and glucu-ronide scutellarin both fit to the two-compartment mod-el. Conclusion The above mentioned method is spe-cific, rapid, sensitive and suitable for the pharmacoki-netic studies of scutellarein and its metabolite.
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Objective To develop a reversed phase high performance liquid Chromatographie (RP-HPLC) analysis system for hydroxysafflor yellow A (HSYA) in rat model of cold coagulation and blood stasis (CCBS), and to investigate the influence of Sappan lignum on the pharmacokinetics of HSYA in CCBS rats. Methods Rat CCBS models were randomly divided into two groups with each containing 6 animals. Rats were orally given Carthami flos extract or Carthami flos extract combined with Sappan lignum (The dosage: 20. 0 g/kg crud drug of Carthami flos). Plasma samples were collected in heparinized tubes from the oculi chorioideae vein at 5, 10, 20, 30, 45, 60, 90, 120, 150, 210, and 270 min after drug administration; and the plasma proteins were precipitated with 20% trichloroacetic acid aqueous solution. Plasma concentrations of HSYA were detected by RP-HPLC at different time points after drug administration. The data were processed by DAS 2. 0 software to calculate the pharmacokinetic parameters. Results Compared with the Carthami flos group, the pharmacokinetic parameters V1/F and CL/ Fof HSYA in the Carthami flos combined with Sappan lignum group were significantly decreased (P<0. 01), and the AUCo-t, Cmax, and t1/2α of HSYA were significantly increased (P<0. 01). Conclusion Sappan lignum can promote the absorption of HSYA in rat model of CCBS and reduce the distribution of HSYA, thus exercise an efficacy-enhancing effect.
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The pharmacokinetics and content of 3H11-8H-HPD in tumor, liver, skin and muscular of tumor-bearing nude mice were reported and compared with free 3H-H'PD. The conjugated molar ratio of 3Hll-3H-HPD was 1 : 27. The 97% antibody activity of conjugate was retained. After 3Hll-3H-HPD or 3H-HPD iv into tumor-bearing nude mice, the pharmacokinetics parameter of blood-drug concentration indicated that the T1/2 of conjugate group was longer than that of 3H-HPD, the elimination rate constant ( Kel ) of conjugat group was larger than that of 3H-HPD group, but the aparent volume of distribution ( Vd ) of the former was less than that of the latter. Tissue distribution study reveald that the radioactivity in tumor tissue of conjugate was increased average 0.9 fold than that of 3H-HPD group. Tumor/liver ratio in both 3Hll-3H-HPD group and 3H-HPD group were 0.66 ? 0.24 and 0.42?0.20, respectively. Contents of 3Hll-3H-HPD in skin or muscular were decreased average 1 fold than that of free 3H-HPD, respectively. The study result was shown the pharmacokinetics characteristic of large molecule conjugate and the targeting action of monoclonal antibody.