Relationships among duration of infusion,dose, dosing interval,and steady-state plasma concentrations during intermittent intravenous infusions: Studies with metronidazole

Relationships among duration of infusion (T), dose, dosing interval (), maximum and minimum plasma drug concentrations at steady state (C_max,ssand C_min,ss, respectively), and the duration of effective plasma concentrations (t_D) during multidose intermittent infusion regimens were studied by computer simulation using metronidazoie as a model drug. Pharmacokinetic parameter values for metronidazole were obtained from the literature and the minimum effective plasma concentration (MEC) was taken as 6.0 g/ ml. Increasing the infusion period of the dose reduces C_max,ss, but increases C_min,ss. If intermittent bolus injection of a given dose of drug results in effective plasma concentrations for the entire dosage interval (i.e., C_min,ss,bolus> MEC), then infusion of that dose over any period (T) will also result in effective concentrations for the entire dosage interval. However, if the dosage is such that C_min,ss,bolus < MEC, the relationships among duration of infusion, dose, dosage interval, and duration of effective plasma concentrations are complex. Therefore a nomogram was developed to allow selection of dose, dosing interval, and infusion period such that C_max,ss and C_min,ss could be maintained within a desired range.     

Correlation between plasma levels of fenofibrate and lipoprotein changes in hyperlipidaemic patients

Summary Eleven hyperlipidaemic patients received two formulations of fenofibrate (differing in in vitro dissolution) in randomized sequence, each for 6 weeks. Formulation N, giving a 2–3-fold higher plasma fenofibrate level compared to R, lowered both the cholesterol and triglyceride levels far more than R. Changes in the total and high density lipoprotein cholesterol levels were not significantly correlated with the fenofibrate level. A highly significant correlation was detected for triglycerides in Type IV patients, and for changes both in very low density lipoprotein (VLDL) cholesterol and triglycerides in the entire group of patients. In conditions of widely distributed steady state levels of an absorbable hypolipidaemic drug, a significant correlation may thus be detected between the plasma level and the reduction of VLDL — associated lipids.     

静脉留置针接真空采血器在内科急危重患者的应用

目的 探讨通过静脉留置针接采血器为急危重患者抽血,以及建立静脉通道,对穿刺成功率、完成时间及病人满意度的影响.方法 将2008年5月-2010年9月我科收治的危重病人220例随机分成两组,观察组采用行外周浅静脉留置针穿刺,同时接真空采血器抽血化验、输液,对照组按常规分别行外周静脉输液及真空采血器抽血化验.观察2组在完成...     

Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension

Summary To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients.We measured the insulin sensitivity index (S_I), determined by the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients [mean body mass index (BMI) 30.2 kg·m^–2] had been on prior treatment with a thiazide diuretic in low dosage and/or a -adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg·m^–2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg once daily in 14 patients who were hypertensive after 8 weeks on the lower dosage.At entry (before placebo), S_I was slightly but not significantly lower in group A than B [2.7 vs. 3.6×10^–4 ml·U^–4·min^–1]; fasting plasma insulin was 13.6 vs. 12.9 U·ml^–1. After 6 weeks on placebo, S_I averaged 3.7 in group A and 4.4×10^–4 U·ml^–1·min^–1 in group B; fasting plasma insulin was 14.6 vs. 15.1 U·ml^–1, and glucose 5.5 vs. 5.5 mmol·l^–1. After 6 months on amlodipine there were no differences in S_I [group A vs. group B, 5.2 vs. 3.8×10^–4 ml·U^–1·min^–1], fasting insulin [13.0 vs. 12.7 U·ml^–1], glucose [5.4 vs. 5.5 mmol·l^–1], serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions. Compared with placebo, amlodipine significantly reduced systolic and diastolic blood pressures. Heart rate, body weight, and 24 h urinary sodium excretion were unaltered.Long-term treatment with amlodipine does not affect insulin sensitivity, circulating insulin or glucose, or lipoprotein metabolism in obese, non-diabetic patients with essential hypertension.     

Effect of low doses of heparin on the plasma binding of phenytoin and prazosin in normal man

Summary The effect of low doses of heparin on the binding of phenytoin and prazosin to plasma proteins was evaluated in four normal subjects. Heparin activates the hydrolysis of triglycerides in plasma. The ensuing increase in non-esterified fatty acids (NEFA) was more marked in vitro than in vivo and increased the free fraction (FF) of phenytoin and prazosin in plasma. The higher FF caused a change in the plasma to whole blood ratio (P/B ratio) of both drugs. The changes in FF and P/B ratio after heparin were small, but could be of significance in pharmacokinetic studies.     

Effects of hydrochlorothiazide and captopril on lipoprotein lipid composition in patients with essential hypertension

Objective: Effective antihypertensive agents may differ in their capacity to reduce cardiovascular risk because they induce potentially atherogenic alterations in lipoprotein composition. Patients: To assess this possibility, the effects of five months' treatment with either hydrochlorothiazide (HCTZ) or the converting enzyme inhibitor captopril (CAPT) on lipoprotein lipid composition were compared in thirty normolipidaemic patients with essential hypertension (EH). Results: The sixteen patients treated with HCTZ showed the expected directional alterations in plasma TG (+31%), HDL₂-C (-16%), and CHOL (+7.6%); in contrast TG and CHOL were unchanged after captopril in fourteen patients and their HDL₂-C declined (-16%). Neither drug altered lipoprotein core lipid composition, but small increases were observed in the HDL₂ sphingomyelin/lecithin ratio after both agents. The plasma free (unesterified) cholesterol (FC) lecithin (L) ratio, a new index of cardiovascular risk, was abnormally increased before treatment and was not altered by either drug. Conclusion: These findings indicate that HCTZ and CAPT treatment have small, but demonstrable effects on lipoprotein surface lipid composition in patients with EH that are confined to the HDL₂ subfraction.Supported by Grant 5446 from the Swedish Medical Research Council and a grant from Bristol Myers-Squibb     

咪达唑仑丙泊酚全麻诱导对老年患者心率和血压的影响

目的:评估联合应用咪达唑仑与丙泊酚全麻诱导对老年患者心率和血压影响.方法:随机选取45例60岁以上ASAⅠ～Ⅱ级行择期外科手术患者分组:Ⅰ组为丙泊酚2.0 mg/kg诱导,Ⅱ组为咪达唑仑0.2 mg/kg诱导,Ⅲ组为丙泊酚1.0 mg/kg联合咪达唑仑0.1 mg/kg诱导,肌松剂均用维库溴胺0.1 mg/kg.采用完全随机双盲设计,记录诱导前后、插管时及插管后的心率和血压的变化,并比较记录结果.结果:三组患者术前心率和血压差异无显著性.插管前后Ⅰ组诱导引起心率变化与Ⅱ组和Ⅲ组比较差异有显著性.插管前后Ⅰ组诱导引起血压变化与Ⅱ组和Ⅲ组比较差异有显著性.结论:联合应用丙泊酚和咪达唑仑诱导,不仅能降低诱导时各自药量,而且对老年患者,特别是对于循环功能耐受较差者更为安全可靠.     

赤软骨黏多糖对家兔血脂水平和凝血时间的影响

目的研究赤软骨黏多糖的降血脂和抗凝血活性。方法观察赤软骨黏多糖对高脂家兔血脂的调节作用和正常家兔全血凝血时间的影响。结果赤软骨黏多糖能显著降低高脂家兔血清总胆固醇(TC)、血清甘油三酯(TG)和血清低密度脂蛋白(LDL-C)含量,提高血清高密度脂蛋白胆固醇(HDL-C)含量,对正常血脂家兔的胆固醇无明显影响,能显著延长家兔全血的凝血时间。结论赤软骨黏多糖具有较强的降血脂和抗凝血活性。     

依折麦布联合阿托伐他汀对高胆固醇血症患者血浆脂蛋白磷脂酶A2水平的影响

目的 探讨依折麦布联合阿托伐他汀治疗高胆固醇血症患者的效果及对血浆脂蛋白磷脂酶A2（Lp-PLA2）水平的影响。方法 选取东莞市第五人民医院确诊的高胆固醇血症患者300例,病例收集时间2017年1月-2017年6月,采用随机数字表法分为联合组（阿托伐他汀20 mg/d+依折麦布10 mg/d）、他汀组（阿托伐他汀20 mg/d）各150例,连续治疗3个月,检测并对比两组治疗前后的血脂水平和Lp-PLA2。结果 治疗前,联合组和他汀组患者的血清总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、Lp-PLA2水平差异均无统计学意义;两组患者治疗后的血清TC、TG、LDL-C、Lp-PLA水平较治疗前均显著的降低,HDL-C水平较治疗前显著升高,同组治疗前后比较差异有统计学意义（P<0.05）;治疗后,联合组患者的血清TC、TG、LDL-C、Lp-PLA2水平较他汀组显著降低,差异有统计学意义（P<0.05）。治疗后,联合组患者显效率为80.00%,总有效率为96.67%,他汀组显效率为69.33%,总有效率为91.33%,两组比较差异具有统计学意义（P<0.05）。联合组患者不良反应发生率8.67%,与他汀组的6.00%比较,差异无统计学意义。结论 依折麦布联合阿托伐他汀治疗高胆固醇血症患者的效果优于单纯使用他汀类药物治疗,并且对血浆LpPLA2水平具有很好的改善作用。     

Effect of pravastatin and cholestyramine on triglyceride-rich lipoprotein particles and Lp(a) in patients with type II hypercholesterolemia

The effects of treatment, on plasma lipids in patients with Type II hypercholesterolemia, for 8–24 weeks was determined with pravastatin (PR) and cholestyramine (CH) given alone or in combination. The first 8 weeks of treatment included a parallel placebo (P) control, while the subsequent period to 24 weeks compared four groups (40 and 80 mg PR, CH, and PR + CH). There were seven to nine patients per group (average age of 58 years). Cholesterol (C) and low-density lipoprotein cholesterol (LDL-C) decreased with PR and CH. There were inconsistent and nonsignificant effects on triglycerides and high-density lipoprotein cholesterol (HDL-C). Apolipoproteins A-I, A-II, B, and Lp(a) were measured, and only Apo-B decreased with drug therapy. Lipoprotein particles characterized by their specific apolipoprotein content were also measured. LpB Cholesterol ester-rich, containing predominantly Apo-B, decreased with PR and CH relative to their respective baselines, but not relative to P. Similarly, triglyceride-rich, LpB_c, a complex lipoprotein particle containing apolipoproteins A-I, A-II, B, C, D, and E decreased relative to baseline, but not with respect to P. This study has further defined the effect of PR and CH on lipids and lipoprotein particles in patients with Type II hypercholesterolemia. These effects might be favorable in relation to reduction of risk factors in atherosclerosis. © 1992 Wiley-Liss, Inc.     

Influence of intralipid on free propofol fraction assayed in human serum albumin solutions and human plasma

AIM: It is generally assumed that only unbound drugs can reach the site of action by diffusing across the membranes and exerting pharmacological effects by interacting with receptors. Recent research has shown that the percentage of free drugs may depend on the total drug concentration. The aim of the paper is to verify whether the mentioned dependence reported for propofol also takes place in plasma and human serum albumin samples in the presence of intralipid-the medium used as a vehicle for propofol infusions and a parenteral nutrition agent. METHODS: Artificial plasma samples and human plasma were spiked with intralipid or ethanolic solutions of propofol. The samples were then assayed for free propofol concentration using ultrafiltration and high performance liquid chromatography with fluorimetric detection. RESULTS: The decrease of the total drug concentration results in free propofol fraction increase, irrespectively of the used type of propofol solvent and sample type. The addition of intralipid causes the lowering of the overall free drug fraction with respect to the samples spiked with ethanolic solutions of the drug. CONCLUSION: The presence of intralipid does not influence the phenomenon of free propofol fraction rise at low total drug concentration. Such a rise cannot be ignored in clinical conditions when the drug is applied for sedative, antiemetic or other low-dosage purposes.     

Protein binding of salicylate and quinidine in plasma from patients with renal failure,chronic liver disease and chronic respiratory insufficiency

Summary The plasma protein binding of a representative acidic drug, salicylate, and a representative basic drug, quinidine, has been studied in patients with several diseases that are sometimes associated with uraemia or a change in serum albumin level. Decreased plasma protein binding of salicylate was observed in plasma from patients with uraemia and liver disease. Low albumin levels in these patients could only account in part for the decreased binding. On the other hand, salicylate binding to plasma proteins appeared to be increased in patients with hypoxia. Decreased plasma protein binding of quinidine was observed in some patients with uraemia and in the majority of patients with liver disease.Results presented in part as an oral communication at the Sixth International Congress of Pharmacology, July 20–25, 1975. Helsinki, FinlandSupported in part by a grant from the Merrell International Research Center     

Effects of oral chlordemethyldiazepam on plasma adrenaline and noradrenaline and cardiovascular reactivity in preoperative patients

Summary In 11 preoperative women, plasma adrenaline (A) concentrations were lower after oral administration of an antianxiety dose (19.25 µg/kg) of chlordemethyldiazepam (Cl-DMDZ) than the predrug values, or those in 12 patients given placebo. No significant differences in supine plasma noradrenaline (NA), blood pressure (BP) and heart rate values were observed. Digital plethysmography showed finger vasoconstriction after placebo and vasodilatation after Cl-DMDZ. A mental arithmetic test caused equivalent rises in plasma A in both groups. Standing caused plasma NA to rise to similar levels in both groups of patients, but the BP decrease was less and there was a markedly lower incidence of orthostatic hypotension in the Cl-DMDZ treated group. It is concluded that the effect of Cl-DMDZ on the release of catecholamines from the peripheral sympathetic system consists essentially of decreasing basal adrenomedullary activity. CL-DMDZ appears to prevent the orthostatic hypotension which occurs when neurosympathetic reflex activation is normal.     

老年2型糖尿病患者糖化血红蛋白与空腹血糖和血脂相关性研究

目的:探讨老年2型糖尿病患者糖化血红蛋白(HbA1c)与空腹血糖(FPG)、血脂的相关性及其意义。方法:对61例老年2型糖尿病患者(糖尿病组)及60例健康老年体检者(对照组)进行HbA1c、FPG、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)测定,对HbA1c及FPG、血脂进行相关性分析。结果:糖尿病组HbA1c,FPG,TC,TG,LDL-C,ApoB明显高于对照组;糖尿病组HDL-C和ApoA1明显低于对照组,HbA1c与FPG,TC,TG,LDL-C,ApoB呈正相关,与HDL-C和ApoA1呈负相关,差异均有统计学意义(P<0.05)。结论:老年糖尿病患者HbA1c与FPG、血脂均有一定的相关性。联合检测HbA1c,FPG和血脂水平对老年糖尿病患者诊断及治疗具有重要意义。     

Effect of simvastatin on plasma lipids,apolipoproteins and lipoprotein particles in patients with primary hypercholesterolaemia

Summary The effect of treatment with simvastatin, a new HMG-CoA reductase inhibitor, has been investigated in 27 patients with primary hypercholesterolaemia.It produced a significant decrease of cholesterol and phospholipids in plasma, LDL and apolipoprotein B-containing lipoproteins. Plasma apolipoproteins B, C-III and E were also significantly lowered. The concentration of lipoprotein particles recognized by monoclonal antibodies (BL₃, BL₅ and BL₇), associated with atherosclerotic disease, was also lowered by the treatment.Lipoproteins LpA-II:A-I were not changed, while LpA-I, which has been suggested to be the protective fraction of the apo A-I-containing lipoproteins, was slightly and inconsistently increased.     

红景天苷对链脲佐菌素诱导糖尿病大鼠血糖、血脂和抗氧化能力的影响

目的研究红景天苷对链脲佐菌素诱导糖尿病大鼠血糖、血脂和抗氧化能力的影响。方法采用ip链脲佐菌素(60mg/kg)制备糖尿病大鼠模型;取造模成功的糖尿病大鼠50只,根据血糖值水平随机分为模型组、二甲双胍(25 mg/kg)组和红景天苷(25、50、100 mg/kg)组,每组10只,并另设对照组。ig给药体积均为1 m L/kg,1次/d,连续给药12周。分别于给药前和治疗后第4、8、12周测定各组大鼠空腹血糖和胰岛素水平。给药治疗12周后,分别称量各组大鼠体质量。测定血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)的水平以及血清中总抗氧化能力(T-AOC)水平,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)的活性和丙二醛(MDA)含量。结果与模型组比较,红景天苷50、100 mg/kg组糖尿病大鼠体质量明显增加,血清中TC水平和MDA含量显著降低(P0.05、0.01);与模型组比较,红景天苷25、50、100 mg/kg组糖尿病大鼠血清中TG、LDL-C水平显著降低且HDL-C水平显著升高(P0.05、0.01),T-AOC水平和SOD、CAT活性均显著升高(P0.05、0.01);与模型组比较,红景天苷100 mg/kg组糖尿病大鼠空腹血糖水平显著降低且胰岛素水平显著升高(P0.01),GSH-Px活性显著升高(P0.05)。结论红景天苷能够有效降低链脲佐菌素诱导糖尿病大鼠的血糖和血脂,并提高机体抗氧化能力。     

Lack of correlation between the acute haemodynamic response to intravenous captopril and plasma concentrations of angiotensin II in patients with chronic cardiac failure

Summary We have given a series of incremental intravenous injections of captopril to ten patients with chronic cardiac failure.Small doses of captopril produced significant changes in pulmonary artery end-diastolic pressure and right atrial pressure, up to a total cumulative dose of captopril of 2.5 mg, after which further injections had no significant effect. There were large changes in systemic vascular resistance and blood pressure up to a cumulative dose of captopril of 5.0 mg, after which the injection of larger doses caused no further significant changes.Small doses of intravenous captopril produced large increases in plasma renin activity and plasma angiotensin I concentrations up to a total cumulative dose of captopril of 1.25 mg, after which there were no significant further changes in either plasma renin activity or plasma angiotensin I concentration. However the plasma concentration of angiotensin II fell more slowly, no further change being recorded after a total cumulative dose of captopril of 10 mg.These results suggest that plasma renin activity is not the only determinant of plasma angiotensin II concentrations.     

The effects of ezetimibe and orlistat,alone or in combination,on high-density lipoprotein (HDL) subclasses and HDL-associated enzyme activities in overweight and obese patients with hyperlipidaemia

Background: High-density lipoprotein (HDL) includes discrete subfractions. HDL exhibits anti-atherogenic properties, which have been partly linked to the activity of HDL-associated enzymes, such as the lipoprotein associated phospholipase A₂ (HDL-LpPLA₂) and paraoxonase-1 (PON1). Objective: We assessed in an open-label randomised study the effect of orlistat and ezetimibe, alone or in combination, on plasma HDL subclasses and HDL-associated enzyme activities in overweight and obese subjects (body mass index > 28 kg/m²) with hypercholesterolemia [total cholesterol > 200 mg/100 ml (5.2 mmol/l)]. Methods: Eighty-six people were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg, three times daily (O group), ezetimibe 10 mg/day (E group) or both (OE group) for 6 months. HDL subfractions were determined using a polyacrylamide gel-tube electrophoresis method. Results: Levels of HDL cholesterol (HDL-C) and apolipoprotein AI did not change significantly in any group. In group O the cholesterol concentration of HDL-2 subclass increased significantly, while the cholesterol of HDL-3 subclass decreased significantly. In groups E and OE HDL-2 subclass did not significantly change, while the cholesterol concentration of HDL-3 subclass decreased significantly. We observed a non-significant decrease in the HDL-LpPLA₂ and PON1 activity in all groups. However, the ratios of both enzyme activities to low-density lipoprotein cholesterol (LDL-C) levels (an index of atherogenicity) significantly increased in all groups. Conclusion: Although HDL-C levels did not change after treatment with orlistat and ezetimibe, alone or in combination, there were alterations of the HDL-2 and HDL-3 subclasses. The activity of HDL-LpPLA₂ and PON1 per mg LDL-C increased significantly in all groups.     

老年糖尿病患者糖化血红蛋白、血糖及血脂的相关性分析

目的探讨老年糖尿病患者血清糖化血红蛋白、血糖以及血脂水平之间的关系。方法选择2009年9月～2013年3月期间,于我院接受治疗的112例老年糖尿病患者及102例老年健康体检者作为研究对象,检测患者血清糖化血红蛋白与血糖及血脂,比较糖化血红蛋白与患者空腹血糖、餐后2h血糖、血脂之间的关系。结果糖尿病患者糖化血红蛋白、血糖及血脂与对照组比较,差异有统计学意义（P〈0．05）;糖尿病患者糖化血红蛋白与空腹血糖、餐后2h血糖及血脂之间存在正相关（P〈0．05）。结论老年糖尿病患者血清糖化血红蛋白、血糖及血脂较正常体检者明显升高,且其糖化血红蛋白的升高与患者的血糖及血脂水平呈一定相关性,检测患者血清糖化血红蛋白对于评价患者血糖、血脂控制效果有意义。     

MDR1C3435T基因多态性对辛伐他汀稳态血药浓度及降脂疗效的影响

目的：研究高脂血症患者MDR1C3435T基因分布及其基因多态性对辛伐他汀稳态血药浓度及降脂疗效的影响。方法：115名高脂血症患者均给予每天20 mg的辛伐他汀治疗4周,在给药前及给药4周后取血样,采用PCR-RFLP（聚合酶链反应-限制性片段长度多态性分析）基因检测技术对MDR1C3435T等位基因进行分析,应用全自动生化分析仪和高效液相色谱仪分别测定血脂及辛伐他汀稳态血药浓度。结果：115名高脂血症患者MDR1C3435T基因型分布符合Hardy-Weinberg遗传平衡（P>0.05）,MDR1C3435T等位基因突变率为40.87％。野生纯合子基因（CC）型组、突变杂合子（CT）型组、突变纯合子（TT）型组之间辛伐他汀稳态血药浓度及降脂疗效无统计学差异（P>0.05）。结论：未发现MDR1C3435T基因多态性对辛伐他汀稳态血药浓度及降脂疗效有明显影响。