Diazepam kinetics in patients with renal insufficiency or hyperthyroidism.

1 Eight patients with end-stage renal insufficiency on maintenance haemodialysis, and seven patients with newly diagnosed hyperthyroidism, received a single intravenous dose of diazepam, followed by blood sampling over the next 7 days. Fifteen healthy volunteer controls, matched with patients for age and sex, were similarly studied. 2 Diazepam half-life in renal failure patients (mean 37 h) was greatly reduced compared to controls (mean 92 h, P less than 0.05) and clearance of total (free plus bound) diazepam correspondingly increased (0.94 v 0.34 ml min-1 kg-1, P less than 0.01). 3 However, differences were largely related to disease-related changes in drug binding and distribution. Mean unbound fraction of diazepam in plasma of renal patients (7.0%) was greatly increased over controls (1.4%, P less than 0.01) and Vd of unbound diazepam greatly reduced (57 v 157 l/kg, P less than 0.01). 4 Clearance of pharmacologically active unbound diazepam (intrinsic clearance) was not significantly different between renal patients and controls (23 vs 30 ml min-1 kg-1). 5 None of the kinetic variables for total or unbound diazepam in thyrotoxic patients differed significantly from those in controls matched for age and sex. 6 End-stage renal failure (or its associated drug therapy) alters diazepam protein binding and distribution, but does not significantly change clearance of unbound drug. Thyrotoxicosis does not influence diazepam kinetics.     

Comparison of long-term renal hemodynamic effects of methyldopa and propranolol in patients with hypertension and renal insufficiency

Studies were carried out in 15 patients with renal insufficiency and hypertension to compare the long-term effects of methyldopa and propranolol on renal hemodynamics. Inulin and PAH clearance measurements were made under baseline conditions and four to six months of antihypertensive therapy with each of the two drugs. Eight of the 15 patients (group I) were started on methyldopa and then switched to propranolol; and in the other seven (group II), the sequence was reversed. There were no statistical differences in blood pressure or inulin or PAH clearances under baseline conditions between the two groups of patients. Blood pressure was controlled equally with the two drugs in combination with furosemide. In group I, there was no significant effect of either antihypertensive drug on inulin clearance, but PAH clearance was significantly higher during methyldopa than propranolol therapy. In group II, the same higher PAH clearance was found with methyldopa, even though the sequence of drug administration was opposite to that of group I. Challenge with iv furosemide resulted in a greater 3-hour natriuresis during methyldopa than propranolol treatment. The observations indicate that glomerular filtration rate (GFR) is not significantly affected by long-term treatment with methyldopa or propranolol but that renal plasma flow (RPF) is higher during treatment with methyldopa in patients with renal insufficiency and hypertension. The higher RPF apparently enhances the acute natriuretic effect of iv furosemide.     

老年心功能不全患者血清地高辛样免疫活性物质测定

采用荧光极化免疫分析法,检测了15例老年心功能不全病人血清地高辛样免疫活性物质(DLIS)浓度。以TDx仪最低检测限0.256nmol·L^-1为阳性检测标准,DLIS检出阳性率为46.7%(7/15),浓度范围0.26～1.52nmol·L^-1,平均浓度0.55±0.44nmol·L^-1;其中1例病人血清DLIS浓度高达1.52nmol·L^-1。结果表明老年心功能不全患者血清中含有较高水平的DLIS;提示对这些患者若因病情需要而用地高辛治疗时,其后的血浓度测定结果易引起“过高估计”,应当谨慎地评价地高辛血浓度测定结果。     

硬膜外分娩镇痛对妊娠期高血压疾病产妇应激反应及肾功能的影响

目的 评价硬膜外分娩镇痛对妊娠期高血压疾病产妇应激反应及肾功能的影响.方法 选择2018年7月至2019年7月在包钢集团第三职工医院经阴道分娩的妊娠期高血压疾病产妇80例,美国麻醉医师协会(ASA)分级Ⅰ或Ⅱ级,年龄范围为22～35岁,初产;足月;单胎,头位.采用随机数字表法将病人分为妊娠期高血压疾病未行任何分娩镇痛组...     

Alprazolam kinetics in patients with renal insufficiency

Alprazolam kinetics following a single 1.0-mg oral dose of alprazolam were compared between seven dialysis-dependent patients with chronic renal failure and seven healthy controls matched for age, sex, and weight. There were no significant differences between patients and controls in alprazolam half-life (11.5 vs. 11.3 hours) or clearance of total drug (1.14 vs. 1.26 ml/min/kg). However, alprazolam free fraction was increased in renal failure patients (35.7% vs. 31.9% unbound, p less than 0.005). Free clearance of alprazolam averaged 23% lower in patients (3.2 vs. 4.1 ml/min/kg), but the difference was not significant. Renal insufficiency has a quantitatively small influence on alprazolam pharmacokinetics.     

肾动脉支架术治疗合并心功能不全的肾动脉狭窄患者的临床研究

目的评价肾动脉支架术治疗合并心功能不全的肾动脉狭窄患者的临床疗效。方法选取2014年3月~2015年3月我院收治的肾动脉狭窄合并心功能不全的患者共280例,随机分为两组,其中观察组140例,选用肾动脉支架术进行治疗,对照组140例,选用经皮球囊血管成形术进行治疗,观察并比较两组患者手术情况、术后血压以及肾功能改善情况。结果观察组患者手术情况以及术后血压、肾功能改善情况均明显优于对照组,比较差异有统计学意义(P0.05)。结论肾动脉支架术对于合并心功能不全的肾动脉狭窄患者有较好的临床疗效,能够有效改善患者肾功能水平,并有效控制病情,值得在临床上予以推广。     

乙型肝炎病毒表面抗原阳性孕妇及其新生儿外周血中乙型肝炎病毒的研究

目的了解乙型肝炎病毒表面抗原(HBsAg)阳性孕妇及其新生儿外周血乙型肝炎病毒(HBV)的感染状况。方法酶联免疫吸附试验(ELISA)法检测新生儿外周血HBsAg;巢式聚合酶链反应(nPCR)检测孕妇及其新生儿外周血HBV-DNA;选择性聚合酶链反应(sPCR)检测孕妇及其新生儿外周血单个核细胞(PBMC)中HBV-DNA,三项指标任一项阳性即判定为新生儿HBV宫内感染。结果HBsAg阳性孕妇血清HBV-DNA阳性率为43.1%(53/123),PBMCHBV-DNA阳性率为30.8%(37/123);新生儿血清HBsAg阳性率为6.5%(8/123),HBV-DNA阳性率为19.5%(24/123),PBMCHBV-DNA阳性率为26.0%(32/123)。新生儿任一项阳性者50例,合计宫内感染率40.6%(50/123)。结论检测PBMCHBV-DNA对血清中HBV-DNA检测进行补充,可以比较准确地反映HBsAg阳性孕妇新生儿宫内HBV感染的状况。     

Pharmacokinetics, safety, and tolerability of solifenacin in patients with renal insufficiency

To evaluate the pharmacokinetics, safety, and tolerability of solifenacin in patients with mild, moderate, or severe renal disease, eighteen patients with renal disease and six healthy volunteers received a single oral dose of solifenacin (10 mg). Pharmacokinetic parameters were assessed from blood samples drawn over a 360-h period. Safety and tolerability were also evaluated. Total mean +/- S.D. exposure (ng . h/mL) to solifenacin in healthy individuals (1190 +/- 403) was increased in patients with renal disease (mild: 1784 +/- 792, moderate: 1559 +/- 555, severe: 2530 +/- 700), and elimination half-life (mean +/- S.D. [h]) was prolonged (healthy: 68.2 +/- 27.2, mild: 89.1 +/- 34.5, moderate: 90.6 +/- 27.3, severe: 111 +/- 38.3). A significant correlation was found between creatinine clearance and pharmacokinetic parameters for exposure and apparent oral clearance. No deaths or serious adverse events occurred during the study. Solifenacin 10 mg was well tolerated in patients with renal disease. Solifenacin displays a higher exposure and a prolonged half-life in patients with renal impairment, especially severe. Therefore, while no special cautions are necessary for patients with mild/moderate renal impairment, patients with severe renal impairment should receive no more than 5 mg solifenacin once daily.     

国产苯磺酸氨氯地平和络活喜治疗慢性肾功能不全合并高血压的对比研究

目的评价苯磺酸氨氯地平(压氏达)和络活喜对慢性肾功能不全合并高血压的患者的治疗效果和安全性。方法慢性肾功能不全(血清肌酐值265~442μmol.L-1)合并高血压患者(坐位DBP 90~105mmHg和/或坐位SBP≤170mmHg)63例被随机分为两组,分别服用压氏达或络活喜5mg每日1次,治疗4周末坐位DBP<80mmHg,且SBP<130mmHg者继续原剂量治疗至8周末;坐位DBP≥80mmHg或SBP≥130mmHg者剂量分别加倍至10mg每日1次治疗至8周末。分别观察患者服药前后血压、心率和肝肾功能等生化指标变化及其不良反应。结果 63例病人均完成8周的临床试验。与试验前比较,用药第4周起,两组患者的收缩压和舒张压均有显著性下降(P<0.01),降压总有效率压氏达组达87%,络活喜组达90%,若以血压为130/80mmHg为靶目标值则:压氏达组8周后12例(37.5%)达标;络活喜组10例(32.3%)达标。两组不良反应轻,试验结束时主要实验室检查指标与试验前比较无统计学差异。结论压氏达5~10mg每日1次是治疗慢性肾功能不全合并高血压的有效药物之一,且安全性好。     

倍他乐克和达利全治疗慢性肾功能不全合并高血压的对比研究

目的:评价倍他乐克和达利全对慢性肾功能不全合并高血压的患者的治疗效果。方法:65例患者被随机分成两组,分别服用倍他乐克片(倍他乐克组)和达利全片(达利全组)比较治疗前及治疗8周后对血压及肾功能影响。结果:达利全组治疗后收缩压平均下降(31.2±4.8)mmHg,舒张压平均下降(11.3±3.8)mmHg,血肌酐浓度平均下降(54.8±9.2)μmol/L。倍他乐克组治疗后收缩压平均下降(30.4±6.3)mmHg,舒张压平均下降(9.2±5.1)mmHg,血肌酐浓度平均下降(8.9±2.8)μmol/L。结论:达利全对慢性肾功能不全合并高血压患者血压及肾功能均有良好效果,而且达利全比倍他乐克有更好的肾功能保护作用。     

Pharmacokinetics of flutamide in patients with renal insufficiency

AIMS: The aim of this study was to determine the pharmacokinetic parameters of flutamide, a nonsteroidal antiandrogenic compound, and its pharmacologically active metabolite, hydroxyflutamide, in renal insufficiency. Haemodialysis (HD) clearance of flutamide and hydroxyflutamide was also determined. METHODS: Pharmacokinetic parameters were assessed for flutamide and hydroxyflutamide in 26 male subjects with normal renal function (creatinine clearance by 24 h urine collection, CLcr, greater than 80 ml min(-1) 1.73 m(-2); n=6) or reduced renal function; CLcr=50-80 (n=7), 30-49 (n=3), 5-29 (n=4), and <5 ml min(-1) 1.73 m(-2)-HD (n=6), following a single, oral 250 mg flutamide dose. Subjects undergoing HD received a second 250 mg dose of flutamide 4 h prior to HD; blood and dialysate were collected during HD to determine dialysability of flutamide and hydroxyflutamide. RESULTS: Cmax, tmax, AUC, t1/2, and renal clearance of flutamide and hydroxyflutamide did not differ between groups. Less than 1% of the dose appeared in dialysate as hydroxyflutamide. No serious adverse events were observed. CONCLUSIONS: Renal function did not affect flutamide nor hydroxyflutamide disposition. HD did not alter hydroxyflutamide pharmacokinetics. Dosing adjustments for renal impairment or HD are not indicated for flutamide.     

Pharmacokinetics of loratadine in patients with renal insufficiency

The disposition of loratadine, a new orally active histamine H1 receptor antagonist and its primary metabolite descarboethoxyloratadine were characterized in adult volunteers with normal renal function (group I), patients with chronic renal failure, i.e., creatinine clearance less than 30 mL/min (group II), as well as chronic hemodialysis patients (group III). The effect of hemodialysis on the disposition of loratadine and descarboethoxyloratadine was also assessed. Subjects in groups I and II were given a single oral 40 mg dose of loratadine while the patients in Group III received two single 40 mg doses of loratadine (during an interdialytic period and just prior to hemodialysis). Loratadine was rapidly absorbed and the decline of plasma concentrations after attainment of the Cmax was biexponential in all subjects. No significant differences in t1/2 beta were observed between the three groups (8.7 +/- 5.9, 7.6 +/- 6.9, 8.6 +/- 1.6 hrs: in groups I, II, and III, respectively). The apparent total body clearance and apparent volume of distribution of loratadine also did not differ significantly among the three groups. No significant differences in the Cmax or tmax of the metabolite were observed. The metabolite AUC infinity 0 however was significantly greater in group II subjects: (212.4 +/- 37.8, 469.5 +/- 95.4, 325.2 +/- 114.6 ng.hr/mL; groups I, II, and III, respectively). No significant relationship was observed between the terminal elimination half-life of loratadine or descarboethoxyloratadine and creatinine clearance. Hemodialysis augmented endogenous clearance by less than 1%. The disposition of loratadine is not significantly altered in patients with severe renal insufficiency nor is hemodialysis an effective means of removing loratadine or descarboethoxyloratadine from the body.     

慢性肾功能不全患者使用头孢吡肟致相关脑病

2例慢性肾功能不全患者因肺部感染使用头孢吡肟致相关脑病.例1,56岁女性患者,给予头孢吡肟2.0 g,2次/d静脉滴注.2 d后患者表情淡漠、认知障碍、行为异常、失眠、肢体不自主震颤.第4天症状加重,脑电图示持续慢波,频繁出现的三相波.立即停用头孢吡肟,行血液透析,2 d后症状好转.例2,22岁男性患者,给予头孢吡肟2.0 g,1次/8 h静脉滴注.用药第5天,出现言语和行为异常,认知障碍、肢体不自主震颤.停用头孢吡肟,行血液透析治疗2 d后,症状消失.     

Ramipril prevents the detrimental sequels of chronic NO synthase inhibition in rats: hypertension,cardiac hypertrophy and renal insufficiency

Inhibition of the angiotensin converting enzyme (ACE) with ramipril was studied in male Wistar rats during long-term inhibition of nitric oxide (NO) synthase by N^G-nitro-l-arginine methyl ester (l-NAME). Chronic treatment with l-NAME in a dose of 25 mg/kg per day over 6 weeks caused myocardial hypertrophy and a significant increase in systolic blood pressure (245 ± 16 mmHg) as compared to controls (155+4 mmHg). Animals receiving simultaneously l-NAME and ramipril were protected against blood pressure increase and partially against myocardial hypertrophy. L-NAME caused a significant reduction in glomerular filtration rate (GFR: 2.56+0.73 ml·kg^–1·min^–1) and renal plasma flow (RPF: 6.93±1.70ml·kg^–1·min^–1) as compared to control (GFR: 7.29±0.69, RPF: 21.36±2.33ml·kg^–1·min^–1). Addition of ramipril prevented l-NAME-induced reduction in GFR and renal plasma flow. l-NAME produced an elevation in urinary protein excretion and serum creatinine and a decrease in potassium excretion which was antagonised by ramipril. L-NAME-induced increase in plasma renin activity (PRA) was further elevated with ramipril treatment. Isolated hearts from rats treated with l-NAME showed increased post-ischaemic reperfusion injuries. Compared to controls duration of ventricular fibrillation was increased and coronary flow reduced. During ischaemia the cytosolic enzymes lactate dehydrogenase and creatine kinase, as well as lactate in the venous effluent were increased. Myocardial tissue values of glycogen, ATP, and creatine phosphate were decreased, whereas lactate was increased. Coadministration of ramipril reversed these effects. l-NAME treatment reduced the cyclic GMP content in urine and renal arteries, and was not changed by additional ramipril-treatment. In the kidney hyalinosis of arterioles and of glomerular capillaries, as well as mesangial expansion and tubular atrophies seen after long-term inhibition of NO synthase were reduced by coadministration of ramipril. In conclusion, long-term ACE inhibition by ramipril prevented l-NAME-induced hypertension and cardiac hypertrophy, and attenuated functional and morphological changes in the kidneys. In addition, cardiac-dynamic and -metabolic deterioration induced by L-NAME was normalised by co-treatment with ramipril. Correspondence to: Max Hropot at the above address     

Lack of endogenous crossreactivity with three digitoxin radioimmunoassays in adults with renal insufficiency

The possibility of interference by apparent digitoxin-like immunoreactive substance (DTLIS) with three radioimmunoassays was studied in patients with renal insufficiency. From each of 25 adult patients with renal insufficiency and 25 age-matched and sex-matched control subjects with normal renal function, a single serum sample was obtained and assayed for digitoxin content by three commercially available radioimmunoassays (GammaCoat, Coat-A-Count, and the Wien assay). Although two of the three assays found measurable concentrations, the difference in apparent digitoxin concentrations between the control subjects and those with renal insufficiency was not significant. Assay interference could not be explained on the basis of differences in age, serum creatinine concentration, or weight. The magnitude of DTLIS interference in relation to the digitoxin therapeutic range appears to be small with the radioimmunoassays used in this study.     

慢性肾功能不全患者肾穿刺活检的风险与价值研究

目的回顾性分析慢性肾功能不全（CRI）患者经皮肾穿刺活检（PRB）的风险与价值。方法对符合条件的50例CRI患者进行PRB,行光镜、免疫组化染色和选择性电镜检测,观察肾穿刺组织肾小球个数、病理类型、诊断以及穿刺并发症。结果肾组织标本合格率为96%。病理类型前三位为增生性肾小球硬化症21例（42%）,IgA肾病（IgAN）9例（18%）,狼疮性肾炎（LN）8例（16%）。PRB后修改诊断5例（10%）,明确病因3例（6%）,诊断修正率为16%,根据病理结果决定治疗方案16例（32%）,治疗方案修正率为26%。并发症以镜下血尿最常见,共48例（98%）,肾周小血肿11例,肾周大血肿2例,腹膜后血肿1例。结论原发性肾脏疾病肾穿后病理结果多为慢性病变,大部分患者的诊断治疗方案不受肾穿刺病理结果的影响,且肾周血肿出现机率较多且较大,偶可合并腹膜后血肿,但狼疮性肾炎表现为慢性肾衰时其肾脏病理的活动指数仍较高,少数病例肾脏病理显示新月体肾炎,仍需应用免疫抑制剂以改善预后。     

肾功能不全患者抗生素的合理应用

肾脏是维持体液和电解质稳态最主要的器官,肾功能不全患者的抗生素体内分布、药物清除率和排泄等药动学参数均可发生不同程度的改变,并可因此影响患者的肾功能。本文综述肾功能不全患者的抗生素合理选用以及针对不同肾功能患者的剂量调整。     

Disposition kinetics of disopyramide in patients with renal insufficiency

The pharmacokinetics of an intravenous injection of disopyramide was studied in five normal subjects and six patients with varying degrees of renal impairment. The elimination rate constant (β) was related to the endogenous creatinine clearance (Cl_cr). However, a decrease in β was not observed until the Cl_cr was reduced below 40 ml min^?1. Below 40 ml min^?1 a linear relationship existed between β and Cl_cr. Similarly, the plasma elimination half-life (t_½β) showed a significant increase when the Cl_cr was less than 30 ml min^?1. Hence, dosage modification for disopyramide is necessary only when renal function is severely impaired. Overall, the apparent volume of distribution in patients with renal insufficiency was reduced to two-thirds of that in normal subjects. Therefore, in patients with Cl_cr less than 40 ml min^?1 both the loading and maintenance dose of disopyramide should be reduced.