Journal Detail Information

1

Cite

Share

Pharmacokinetics and relative bioavailability of telmisartan in male healthy Chinese volunteers

Junxian YU ; Yindi ZHANG ; Haitong ZHUO ; Jianping SHEN ; Xiaoxing YIN

Chinese Journal of Clinical Pharmacology and Therapeutics.2005;10(4):417-420.

AIM: To compare pharmacokinetics and relative bioavailability of telmisartan capsule (T) and telmisartan tablet(R). METHODS: 20 male healthy Chinese volunteers were enrolled in a randomized two-way crossover designs with a single-oral dose study(80 mg once per day for each preparation). The plasma telmisatan concentration was determined by HPLC- fluorescence detector. Plasma levels of telmisatan were followed up to 96 h. Area under the telmisartan concentration time curve was calculated by variance analysis and the bioequivalent was determined by two one-side t-test. RESULTS: A two-compartment model was adopted in telmisartan plasma concentration-time data analysis. The pharmacokinetic parameters of T and R in single-dose study including Cmax (μg·L-1), Tmax (h), T1/2β (h), MRT(h), AUC0-92(μg·h·L-1) were as following: 456±253 and 760±314, 1.61±0.71 and 1.08±0.36, 22.39±6.29 and 21.08±5.24, 27.02±6.23 and 24.27±5.79, 3454±1050 and 3635±1300, respectively. Statistically significant differences were observed between the parameter values of the two products in Cmax and Tmax; whereas there was no statistically significant difference between AUC0-∞μg·h·L-1 (3601±1095 and 3767±1399). The relative bioavailability for T was 97.28%±12.74%. CONCLUSION: The test telmisartan capsule is bioequivalent to the reference tablet.

2

Cite

Share

Changes of three COX isoforms expression after formalin induced inflammatory pain in brain and analgesic effects of different COX inhibitors

Zhihong LU ; Xiaoyun XIONG ; Jingru MENG ; Zhenguo LIU ; Zhipeng WANG ; Qibing MEI

Chinese Journal of Clinical Pharmacology and Therapeutics.2005;10(5):499-504.

AIM: To compare the expression of three cyclooxygenase (COX) isoforms in the process of inflammatory pain and evaluate the analgesic effects of different protocols about usage of COX inhibitors on inflammatory pain. METHODS: Formalin was injected subplantarly to mice to induce inflammatory pain. The expression of COX-1, COX-2 and COX-3 was evaluated by radioimmunoassay and RT-PCR, respectively. For the analgesic effect assay, animals were divided into 5 groups including control, SC, NS, IN and NS + SC group. The former 4 spectively. In the NS + SC group, animals received NS398 during the first 1 month and SC-560 during the second month in the NS + SC group. RESULTS: The expression of COX-1 was higher at the late phase while that of COX-2 was higher at the early phase of inflammatory pain. The expression of COX-3 did not significantly change in the process of inflammatory pain. Additionally,behavioral assessment showed that using COX-2 inhibitors at the early phase followed by COX-1 inhibitors at the late phase could get better analgesic effect on inflammatory pain compared with single using COX-1 selective or COX-2 selective inhibitors. CONCLUSION: In brain, the expression of COX-2 increases rapidly in the inflammatory pain process while COX-1 expression does not increase till the late phase. Brain COX-3 is poorly involved in the inflammatory process. Combined use of COX-1 and COX-2 selective inhibitors may be a better protocol in inflammatory pain treatment.

3

Cite

Share

Assessment of coronary flow velocity pattern during no-reflow phenomenon by transthoracic Doppler echocardiography combined with administration of Albunex

Lixin CHEN ; Xinfang WANG ; Mingxing XIE ; Xiangming ZHU ; Ying WU

Chinese Journal of Clinical Pharmacology and Therapeutics.2005;10(3):270-275.

AIM: To validate the alternations of flow velocity patterns in the infarct-related artery (IRA) during no-reflow phenomenon in a canine model of acute myocardial ischemia and reperfusion by transthoracic Doppler echocardiography (TTDE) combined with myocardial contrast echocardiography (MCE) by means of administration of Albunex. METHODS: Nineteen dogs first underwent 60 min myocardial ischemia and then followed by 60 min,120 min and 180 min reperfusion ( n = 6, 6 and 7, respectively). The perfusion defect area determined by MCE at 60 min myocardial ischemia was regarded as risk area (RAMCE). The perfusion defect area defined by MCE after reperfusion was considered as no-reflow area (NRAMCE). The ratio between NRAMCE and RAMCE ≥ 25 %was regarded as the development of no-reflow phenomenon and the ratio of NRAMCE to RAMCE＜25% was considered as the myocardial reflow. The coronary flow velocity parameters in IRA were determined through TTDE. RESULTS: Two dogs died during experiment and the remaining seventeen dogs completed throughout the procedure.There were seven dogs in reflow group and ten dogs in noreflow group. No significant difference was present in reflow group between at baseline and at 60 min reperfusion in systolic peak velocity (PVs), systolic velocity time integral (VT Is), corrected systolic flow duration (cFDs),diastolic peak velocity (PVd), diastolic velocity time integral (VT Id), corrected diastolic flow duration (cFDd),diastolic deceleration rate (DDR), corrected diastolic deceleration duration (cDDD) (P＞0.05), however, a significant difference was found in no-reflow group between at baseline and at 60 min reperfusion in PVs,VTIs, cFDs, PVd, VTId and cFDd (P＜0.05). The most marked alterations during diastolic phase were the increase of DDR and reduction of cDDD. CONCLUSION: The impaired microvasculature may profoundly affect the coronary flow velocity pattern in the IRA. The increase in microvascular resistance and decrease in coronary perfused pressure can contribute to the changes.Transthoracic Doppler echocardiography combined with MCE has the capability of noninvasive assessment of coronary flow velocity pattern in the IRA during no-reflow phenomenon.

4

Cite

Share

Dynamic changes of ATPases and NOS activities and NO production at different anesthesia phases of thiopental and propofol anesthesia

Hongliang LIU ; Tijun DAI ; Shanglong YAO

Chinese Journal of Clinical Pharmacology and Therapeutics.2005;10(3):265-269.

AIM: To investigate the dynamic changes of ATPases and NOS activities and NO production at different anesthesia phases using thiopental and propofol andifferent anesthetic phases (induction, anesthesia, restoration, and awake), the activities of NOS and ATPase and NO production in cortex and brain stem were meagroup. RESULTS: Ca2+ -ATPase and Na+ ,K+ -ATPase activities in the cortex and brain stem were significantly decreased after administration ofthiopental and propofol,especially at induction, anesthesia, or even restoration phase of thiopental group (P＜0.05, P＜0.01) and at anesthesia phase of propofol group (P＜0.05). NOS activities and NO production decreased from induction to restoration phase with thiopental and propofol anesthesia (P＜0.01). The parameters were returned near to the normal at awaken phase. CONCLUSION: Activities of ATPases and NOS and the production of NO may mediate the anesthesia effects of thiopental and propofol in the rat cortex and brain stem.

5

Cite

Share

Efficacy and safety of liduofen in treatment of patients with osteoarthritis of knee joint

Anxiu SUN ; Zonggui WANG

Chinese Journal of Clinical Pharmacology and Therapeutics.2005;10(2):154-157.

AIM: To investigate the efficacy and safety of liduofen in the treatment of patients with osteoarthritis of the knee joint. METHODS: A randomized, double-blind, parallel-controlled, multi-centre study was adapted to compare the efficacy and safety between liduofen and Olfen-75 in 136 patients. Patients were randomly assigned into two groups: liduofen group which was received 75 mg (diclofenac) Liduofen injection (n=69) once a day for seven days and Olfen group which was received 75 mg (diclofenac) Olfen-75 injection (n=67) once a day for seven days. RESULTS: After the treatment, similar improvements for rest pain, pain on exercise, swelling of joint, pressing pain of joint, knee joint bend extend function measured using a 10 cm visual analogue scale was performed in two groups. In Olfen-75 group, the rate of efficacy was 62.69% in the 3rd day, 95.76% in the 5th day and 97.88% in the 7th day. While in liduofen group, the rate of efficacy was 57.97% in the 3rd day, 93.87% in the 5th day and 96.94% in the 7th day. In liduofen and Olfen-75 groups, the progressive rates were 56.72% and 55.07%, respectively. The total improvement rates were 89.85% and 92.54% respectively (P＞0.05), and the rates of side effects were 0% and 1.49%, respectively (P＞0.05). CONCLUSION: Liduofen is an effective and safty drug inthe treatment of patients with osteoarthritis of the knee joint. There is no significant difference on efficacy and safety between the two groups using liduofen and Olfen-75.

6

Cite

Share

Dose-response and control of adeno-associated viral vectors based preclinical and clinical gene therapy

Qizhao WANG ; Yinghui LV ; Ruian XU

Chinese Journal of Clinical Pharmacology and Therapeutics.2008;13(10):1182-1194.

Human gene therapy needs to express exogenous DNA at the targeting cells,producing a practical and efficient therapeutic dosage at an approp-riate time(quantitative pharmacology)with a safe man-ner.Recombinant adeno-associated virus(rAAV)Vec-tom possess a number of properties and recent progress in rAAV production made it rapidly become the reagent of choice for therapeutic gene tmasfer.Over 60 clinical trials of gene therapy based on rAAV have been carried out.The dose response reaction between rAAV vectors and gene expression activity or clinical outcome is one of major aspects of these trials.Most studies showed that vector genomes(vg)and gene expression had a concentration-dependent relationship during a certain scope.However,gene expr~sion Can be afffected by viral serotypes,tissue tropisms,cell targeting,drug regulation,injection route,age and sex,etc.Thus,these aspects should be carefully comidered by scienti-sts,pharmacologisis and physicians during animal ex-periments or clinical trails.KEY WORDS gene therapy;viral vector;dose-re-sponse;quantitative pharmacology;clinical thempy

7

Cite

Share

Optimizing method of Michaelis-Menten pharmacokinetic parameters of bolus intravenous administration

Yinfa SU

Chinese Journal of Clinical Pharmacology and Therapeutics.2004;0(10):-.

As the fitting value of Michaelis-Menten pharmacokinetic parameters K_m and V_m of accurate linear regress (ALR) or improved Hanes-Woolf method has some deviation, a optimizing method of K_m and V_m was used in this paper. The result of ALR or improved HanesWoolf method was taken as the primary value of parameters(V_m and K_m,). The method combined Runge-Kutta algorithm with program solution in Excel software (RK-PS) was used to minimum weighting residual square sum [∑ (c-c~*)2/c] of concentration. The primary value of parameters was optimized. The RK-PS method was better than ALR method and improved Hanes-Woolf method in two examples.

8

Cite

Share

Effects of aspirin on promoter activities of human MMP-9 gene

Yong QI

Chinese Journal of Clinical Pharmacology and Therapeutics.2004;0(10):-.

0.05). CAT expression of pCAT 1.28 and pCAT 0.65 are 2 and 1.6 times as high as the control group's. CAT expression of pCAT 1.28, pCAT 0.65 and pCAT 0.54 were 2.5, 2.2 and 1.3 times as high as the control group's. Aspirin inhibited the promoter activities of pCAT 1.28, pCAT 0.65. And the inhibition of Aspirin was reversed by PMA. CONGCLUSION:Aspirin can inhibit the expression of human MMP-9 gene in the transcriptional level and can inhibit the formation and development of prostatic carcinoma.

9

Cite

Share

Quantitative design of clinical scheme of combination drug therapy

Qingshan ZHENG

Chinese Journal of Clinical Pharmacology and Therapeutics.1999;0(04):-.

Aim To show the performance of the weighted modification method in the clinicaldesign of combination drug therapy. Methods A scheme combined by Drug1, Drug2and Drug3 was used to treat infants with iron deficiency anemia for 2 wk in a hypo-thetical clinical trial. Thirty-six infants were randomly into 6 compound groups. Threedrugs in the scheme were divided into 6 dose levels, which were evenly distributed to the6 groups according to the weighted modification method. The increased Hb (?Hb) wasrecorded at 2, 3, 4 wk after the treatment (po ). The dose-effect data at 4 wk wereanalyzed by the method, and then the doses in scheme were modified by the analyticresult. The modified doses in the scheme would be further demonstrated. ResultsDrug1 and Drug2 were principal drugs, but Drug1 had larger contribution to the com-bined effect (△Hb) than Drug2. Drug3 had little effect. There was a strong synergismbetween Drug1 and Drug2 with the weighted coefficient (b1) = 2. 636 (P

10

Cite

Share

Telomerase and telomerase inhibitors

Zhaoning JI ; Guoqin LIU

Chinese Journal of Clinical Pharmacology and Therapeutics.1999;0(04):-.

DISPLAY OPTIONS

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share