氯沙坦对家兔环孢素A药代动力学影响的研究

目的研究氯沙坦对家兔环孢素A（CsA）药代动力学的影响。方法采用荧光偏振免疫法（FPIA法）测定6只家兔合用氯沙坦前后CsA的血药浓度,并对2组（单用CsA组和合用氯沙坦组）药代动力学参数进行分析。结果合用氯沙坦组的CsA峰浓度（Cmax）、曲线下面积（AUCν0-24）均显著升高（P〈0．01）,血浆清除率（cL）及表观分布容积（V）均显著降低（P〈0．05或P〈0．01）,其余药动学参数无显著性变化（P〉0．05）。结论合用氯沙坦可升高CsA的血药浓度,临床上其与CsA合用需监测CsA的血药浓度,保证治疗的安全有效。     

氯沙坦对兔体内环孢素A药代动力学的影响

目的研究氯沙坦对兔体内环孢素A（CsA）药代动力学的影响。方法采用荧光偏振免疫法测定6只家兔单用及合用氯沙坦后CsA的血药浓度,并对两组动物药代动力学参数进行统计学分析。结果合用氯沙坦后CsA的峰浓度（Cmax）、药时曲线下面积（AUC）显著升高,清除率（CL）及表观分布容积（V）显著降低,其余药代动力学参数无显著性变化。结论氯沙坦可升高CsA的血药浓度,临床上两药合用必须监测CsA的血药浓度,保证治疗安全有效。     

肾移植受者口服环孢素A药代动力学的性别差异

目的 :研究性别差异对肾移植受者口服环孢素A(CsA)的药代动力学影响。方法 :选择肾移植术后 2wk肝肾功能稳定的患者 41名 ,男 2 1名 ,女 2 0名。口服环孢素剂量 6mg·kg- 1·d- 1,用FPIA方法检测各时间点CsA全血浓度并用 3p87药动学程序拟合CsA药动学参数。结果 :男性和女性口服CsA的主要药动学参数分别为 :tmax(h) :2 .9± 1 .0和 2 .2± 0 .9,Cmax(mg·L- 1) :1 .0± 0 .4和 0 .9± 0 .5 ,Cmin(mg·L- 1) :0 .2 0± 0 .0 9和 0 .1 7± 0 .1 1 ,T1 2 (a) (h) :0 .8±0 .6和 0 .7± 0 .5 ,T1 2 (e) (h) :3 .0± 1 .2和 2 .8±0 .8,AUC0 - 12 (mg·L- 1·h- 1) :5.5± 1 .4和 4 .5± 1 .7,CL F(L·h- 1) :40± 2 5和 47± 35 ,V F(C) (L) :1 59±1 0 8和 1 72± 92。结论 :肾移植患者口服CsA的AUC0 - 12 和tmax具有性别差异     

大黄素对环孢素A在大鼠体内的药代动力学

目的评价中药成分大黄素对大鼠灌服环孢素A(CsA)的药代动力学。方法 60只雄性SD大鼠按体重进行随机分为5组,分别灌服CsA+60 mg.kg-1高剂量蒸馏水;CsA+30 mg.kg-1低剂量酮康唑;CsA+大黄素(60 mg.kg-1);CsA+大黄素(30 mg.kg-1);1～3 d大黄素,第4 d灌服CsA+大黄素。用HPLC-MS法测定全血中CsA的浓度,kinetica软件计算主要药代动力学参数,用SPSS17.00进行统计学分析。结果阳性对照组与空白对照组药代动力学参数除吸收速率外均有显著性差异;高剂量大黄素组使其较快达到峰浓度(P<0.05);低剂量大黄素组药代动力学参数与空白对照组比较无显著性差异;服用3 d大黄素后,最后1 d灌服CsA+大黄素组的吸收速率和峰浓度与空白对照组比较有显著性差异(P<0.05)。结论大黄素对CsA的生物利用度和代谢无明显影响。     

肾移植病人口服环孢素的药代动力学

本文用HPLC法测定环孢素的全血浓度,对8例异体肾移植病人口服环孢素后的药代动力学特性进行研究。病人在肾移植后用环孢素的时间为47天到11个月,平均给药剂量为8.26±1.41 mg/kg·d(5.88～10.0mg/kg·d),每12h一次。病人常规监测血样本300余次。测得病人的环孢素药代动力学参数:峰浓度(Cmax)664.9±87.5 ng/ml,达峰时间(Tmax)3.27±1.07h;t¹/₂β13.53h(6.13～44.3h)。     

环孢素A血药浓度的监测与药动学研究

环孢素（Ａ（Ｃｙｃｌｏｓｐｏｒｉｎ Ａ，ＣｓＡ）是目前用于器官移植中预防排斥反应和治疗自身免疫性疾病的最好的免疫抑制药物。可用于骨髓、肝脏、心脏和肾脏移植的排异反应，对于预防胰、角膜、心、移植后的排异反应也获成功。对某些生疾病也有效，在我国已膛渐开始使用。由于它具有较大的肾生，药动学参数个体差异较大，因此世界多数器官移植中心认为在环孢素Ａ治疗中血药浓度的监测和药动学研究，对预防移植器排异反应和减少     

联苯双酯对兔体内环孢素A药代动力学影响的实验及临床观察

目的:考察联苯双酯(BFD)与环孢素A(CsA)在兔体内并用后,对CsA动力学过程的影响.方法:用高效液相色谱法测定6只兔在单用CsA和并用BFD后CsA的血药浓度,并进行动力学参数的计算与比较.结果:CsA与BFD并用后,CsA在兔体内的血浓度普遍降低,表观分布容积及清除率显著增大(0.05＞P＞0.01),AUC明显小于单用CsA(0.05＞P＞0.01)时的AUC,其余的参数无统计学差异.通过临床观察,验证了肾移植患者在同时服用CsA和BFD后造成体内CsA全血药物浓度降低,与兔实验结果一致.结论:BFD可明显降低CsA的血药浓度,不宜与CsA联用.     

川芎嗪对大鼠灌服环孢素A药代动力学的影响

目的研究中药成分川芎嗪(TMP)对大鼠灌服环孢素A(CsA)药代动力学的影响。方法40只雄性SD大鼠按体重进行随机区组设计，分为4组。试验d 1，每只大鼠灌服CsA(10 mg·kg^-1)后，于0，1，2，3,4，6，8，12，24，36和48 h从尾静脉处采血0.2～0.25 mL。然后各组大鼠从试验的d 4到d 8进行不同的预处理，即每日分别灌服蒸馏水、维拉帕米(Ver)、低剂量和高剂量的TMP。d 9时各组大鼠单次合用CsA(10 mg·kg^-1)和上述的各种化合物后，按d 1的时间点采样。用HPLC法测定全血中CsA的浓度，计算其主要药代动力学参数并进行统计学分析。结果合用蒸馏水组的CsA药代动力学参数前后无显著性差异；Ver预处理并合用后，CsA的AUC^{0-48 h}和C_max均显著增加(P<0.01和P<0.05)，T^1/2β显著延长(P<0.05)，CL显著降低(P<0.05)，而T_max和V的变化无统计学差异。低剂量TMP预处理并合用后，CsA的AUC^{0-48 h}和C_max有增加的趋势，但无统计学差异，其余药代动力学参数的变化也无统计学的差异。高剂量TMP预处理并合用后，CsA的AUC^{0-48 h}和C_max均有显著的增加(P<0.01)，但其他药代动力学参数的变化无统计学差异。结论高剂量的TMP能显著提高CsA的灌服生物利用度，但对CsA的体内消除过程几乎没有影响。     

甘草提取物对大鼠体内环孢素药代动力学的影响

目的:研究甘草连续给药7 d对环孢素在大鼠体内的药代动力学影响。方法:12只大鼠随机分为生理盐水对照组和甘草实验组,甘草实验组予甘草提取物(0.5 g/kg,1次/d)连续给药7 d,第8天晨两组均予环孢素灌胃给药后按时间点连续采样,采用荧光偏振免疫分析法测定环孢素的血药浓度,计算并比较主要药动学参数。结果:对照组和实验组的环孢素主要药动学参数Cmax、tmax、t1/2、AUC0-48 h、AUC0-∞、平均滞留时间(MRT)、药物清除率(CL/F)、表观分布面积(V/F)差异均无统计学意义(P>0.05)。结论:甘草连续给药7 d后不影响环孢素在大鼠体内的药代动力学。     

厄贝沙坦达稳态时对兔体内环孢素A药动学的影响

目的:研究厄贝沙坦对家兔体内环孢素A(CsA)药动学的影响。方法:采用荧光偏振免疫法测定6只家兔单用CsA及合用厄贝沙坦后CsA的血药浓度,并对2组药动学参数进行统计学分析。结果:合用厄贝沙坦后CsA的峰浓度(Cmax)显著升高(P<0.01),曲线下面积(AUC0→24)显著增大(P<0.01),血浆清除率(CL)及表观分布容积(V)显著降低(P<0.05),其余药动学参数无显著性变化。结论:厄贝沙坦可升高CsA的血药浓度,建议临床上两药合用时须监测CsA的血药浓度,保证治疗安全有效。     

Pulmonary pharmacokinetics of cyclosporin A liposomes

The development of liposomal formulations for aerosol delivery with jet nebulizers has expanded the possibilities for effective utilization of aerosol based therapies in the treatment of pulmonary diseases. The property of sustained release or depot effect of liposomes has been studied using different tracer molecules to monitor absorption and clearance of liposomes from the lung. With liposomal drug formulations, few studies have simultaneously monitored phamacokinetics of both the phospholipid carrier and the therapeutic agent. We have developed a cyclosporin A (CsA)-dilauroylphosphatidylcholine (DLPC) liposomal formulation for aerosol delivery to the lung. Recent studies of CsA-liposomes have reported that CsA displays a unique property of rapid bilayer membrane exchange with dissociation between CsA and its liposome carrier in vivo following intravenous delivery. The purpose of this study was to determine the pharmacokinetics of both CsA (determined by HPLC) and liposomal carrier (labeled with ^99mtechnetium (^99mTc)) to study potential dissociation after delivery to normal mouse lungs. Furthermore, the effects of pulmonary inflammation on the clearance of CsA-DLPC liposomes were compared with ^99mTc labeled human serum albumin (HSA). Results indicate that ^99mTc-DLPC liposome carrier is retained up to 16.9 times longer than the CsA half-life in normal lung and 7.5 times longer in inflamed lungs. Similar values were obtained for ^99mTc-labeled albumin (14.8 times for normal CsA half life (6.8 times in inflamed lungs)). These pharmacokinetic results help to delineate the most effective therapeutic regimens for pulmonary CsA-liposome aerosol delivery.     

Clinical pharmacokinetics of losartan

Losartan is the first orally available angiotensin-receptor antagonist without agonist properties. Following oral administration, losartan is rapidly absorbed, reaching maximum concentrations 1-2 hours post-administration. After oral administration approximately 14% of a losartan dose is converted to the pharmacologically active E 3174 metabolite. E 3174 is 10- to 40-fold more potent than its parent compound and its estimated terminal half-life ranges from 6 to 9 hours. The pharmacokinetics of losartan and E 3174 are linear, dose-proportional and do not substantially change with repetitive administration. The recommended dosage of losartan 50 mg/day can be administered without regard to food. There are no clinically significant effects of age, sex or race on the pharmacokinetics of losartan, and no dosage adjustment is necessary in patients with mild hepatic impairment or various degrees of renal insufficiency. Losartan, or its E 3174 metabolite, is not removed during haemodialysis.The major metabolic pathway for losartan is by the cytochrome P450 (CYP) 3A4, 2C9 and 2C10 isoenzymes. Overall, losartan has a favorable drug-drug interaction profile, as evidenced by the lack of clinically relevant interactions between this drug and a range of inhibitors and stimulators of the CYP450 system. Losartan does not have a drug-drug interaction with hydrochlorothiazide, warfarin or digoxin. Losartan should be avoided in pregnancy, as is the case with all other angiotensin-receptor antagonists. When given in the second and third trimester of pregnancy, losartan is often associated with serious fetal toxicity. Losartan is a competitive antagonist that causes a parallel rightward shift of the concentration-contractile response curve to angiotensin-II, while E 3174 is a noncompetitive "insurmountable" antagonist of angiotensin-II. The maximum recommended daily dose of losartan is 100mg, which can be given as a once-daily dose or by splitting the same total daily dose into two doses. Losartan reduces blood pressure comparably to other angiotensin-receptor antagonists. Losartan has been extensively studied relative to end-organ protection, with studies having been conducted in diabetic nephropathy, heart failure, post-myocardial infarction and hypertensive patients with left ventricular hypertrophy. The results of these studies have been sufficiently positive to support a more widespread use of angiotensin-receptor antagonists in the setting of various end-organ diseases. Losartan, like other angiotensin-receptor antagonists, is devoid of significant adverse effects.     

Effect of ponsinomycin on cyclosporin pharmacokinetics

Summary The influence of treatment with ponsinomycin, a new macrolide antibiotic, on the pharmacokinetics of cyclosporin A has been studied in 10 renal transplant patients. The pharmacokinetics of cyclosporin A was investigated at steady state, before and during treatment with ponsinomycin.On average, the blood levels of cyclosporin A were doubled by the macrolide, possibly due to a decrease in elimination or/and to an increase in absorption.Ponsinomycin should be use very carefully in patients treated with cyclosporin A.     

Clinical pharmacokinetics of cyclosporin

Cyclosporin (cyclosporin A) is a unique immunosuppressant used to prevent the rejection of transplanted organs and to treat diseases of autoimmune origin. Therapeutic drug monitoring of cyclosporin is essential for several reasons: wide variability in cyclosporin pharmacokinetics has been observed after the oral or intravenous administration of the drug. The variability in the kinetics of cyclosporin is related to a patient's disease state, the type of organ transplant, the age of the patient and therapy with other drugs that interact with cyclosporin; maintaining a blood concentration of cyclosporin required to prevent rejection of the transplanted organ; minimising drug toxicity by maintaining trough concentrations below that which toxicity is most likely to occur; and monitoring for compliance since patient non-compliance with drug regimens is a significant reason for graft loss after 60 days. Clinical monitoring and pharmacokinetic studies of cyclosporin can be performed using different biological fluids (plasma, serum or whole blood) and different analytical techniques (radioimmunoassay or high pressure liquid chromatography). The available analytical methods provide different results when using blood, plasma, or serum. Comparison of therapeutic ranges and pharmacokinetic parameters should be made with careful attention given to the method of cyclosporin analysis. Following oral administration, the absorption of cyclosporin is slow and incomplete. Peak concentrations in blood or plasma are reached in 1 to 8 hours after dosing. The bioavailability of cyclosporin ranges from less than 5% to 89% in transplant patients; poor absorption has frequently been observed in liver and kidney transplant patients and in bone marrow recipients. Factors that affect the oral absorption of cyclosporin include the elapsed time after surgery, the dose administered, gastrointestinal dysfunction, external bile drainage, liver disease, and food. Cyclosporin is widely distributed throughout the body. Following intravenous administration, the drug exhibits multicompartmental behaviour. The volume of distribution (whole blood; HPLC) ranges from 0.9 to 4.8 L/kg. Cyclosporin is highly bound to erythrocytes and plasma proteins and has a blood to plasma ratio of approximately 2. In plasma, approximately 80% of the drug is bound to lipoproteins. The distribution of cyclosporin in blood can be affected by a patient's haematocrit and lipoprotein profile. Cyclosporin is extensively metabolised, primarily by mono- and dihydroxylation as well as N-demethylation, and is considered a low-to-intermediate clearance drug.(ABSTRACT TRUNCATED AT 400 WORDS)     

环孢素A对兔体内伊曲康唑及其代谢物羟基伊曲康唑的药动学影响

目的:探讨环孢素A(CsA)与伊曲康唑在兔体内合用后,环孢素A对伊曲康唑ITZ和羟基伊曲康唑(OH-ITZ)的药动学影响。方法:24只新西兰兔随机分成3组进行平行对照实验。第1组为健康对照组,单侧耳缘静脉注射(ITZ);第2组为免疫力低下组,单侧耳缘静脉注射ITZ;第3组为免疫力低下组,于免疫抑制兔中单侧耳缘静脉分别注射CsA和ITZ。用高效液相色谱-荧光法测定血浆中ITZ和OH-ITZ的浓度,采用Winnolin非房室模型计算药动学参数。结果:免疫力低下兔组中,第3组与第2组比较,ITZ的药动学参数差异无显著性(P>0.05),而OH-ITZ的AUC0-48 h明显增加,即(4 753.1±1 241.7)h.μg.L-1 vs(7 134.1±3 111.1)h.μg.L-1,P<0.05;峰浓度Cmax也明显变大,即(299.4±60.5)μg.L-1 vs(472.9±267.8)μg.L-1,P<0.05,但达峰时间tmax和半衰期t1/2则无统计学意义。第1组与第2,3组比较,ITZ t1/2明显增大,即分别(12.3±5.5)h vs(7.0±1.6)h vs(8.0±3.8)h,P<0.05。...     

氯沙坦对兔动脉粥样硬化形成的影响

目的：观察氯沙坦对高脂兔动脉粥样硬化形成的影响。方法：建立高脂兔动脉粥样硬化模型,治疗组在高脂饮脂的同时给予氯沙坦治疗,3mo后观察兔主动脉及冠状动脉粥样硬化形成的情况及测定血脂水平。结果：治疗组主动脉粥样硬化面积小于高脂组,冠状动脉病变较后者轻微,各组间血脂水平差异无统计学意义。结论：氯沙坦能抑制高脂血症所造成的兔动脉粥样硬化病变的形成,其作用并非通过降低血脂水平。     

The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers

The effects of berberine (BBR) on the pharmacokinetics of ciclosporin A (CsA) were examined in healthy volunteers. Six healthy male volunteers were orally treated with 0.3 g BBR, twice daily for 10 days. Pharmacokinetic investigations on CsA at 6 mg/kg were done both before and at the end of the BBR treatment period. Another six healthy male volunteers were involved in the pharmacokinetic study with 3 mg CsA/kg, in which the subjects orally received the second single dose of 3 mg CsA/kg, followed by a single oral dose of 0.3 g BBR. The blood CsA concentrations were determined by fluorescence polarization immunoassay. In the pharmacokinetic study with 6 mg CsA/kg, BBR caused no significant changes in the pharmacokinetic parameters of CsA. However, in the trial with 3 mg CsA/kg, the average percentage increase in area under the blood concentration-time curve of CsA was 19.2% (P < 0.05) and the mean C12 increased to 123 microg/l from 104 microg/l (P < 0.05), without altering elimination half-life (t(1/2)), maximum blood drug concentration (Cmax), time to Cmax (tmax), apparent oral clearance (CL/F). The present results suggest that BBR can increase the oral bioavailability of CsA at the dosage of 3 mg/kg. The BBR-mediated increase in CsA bioavailability may be partly attributed to a decrease in liver and/or intestinal metabolism through the inhibition of CYP3A4 in the liver and/or gut wall. The BBR-induced increase in emptying time of stomach and small intestine might be another reason for the increase in CsA bioavailability. However, the speculation should be proved by further investigation.