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.     

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.     

Alfentanil kinetics in renal insufficiency

Summary Alfentanil 100 µg/kg was administered as an i.v. bolus to 9 patients with severe chronic renal dysfunction (creatinine clearance 1.0±1.2 ml/min) requiring regular haemodialysis. Plasma alfentanil concentrations were measured by a specific radioimmunoassay. Individual plasma concentration-time curves were fitted to a two-compartment open model. Mean distribution and elimination half-lives were 3.7 min and 58 min, respectively. The apparent volumes of distribution of the central compartment and the total volume of distribution at steady-state were 91 ml/kg and 304 ml/kg, respectively. Alfentanil plasma clearance was 5.3±2.5 ml/min/kg. All the patients tolerated alfentanil well and no side-effects nor delayed recovery were observed.     

Nalidixic acid kinetics in renal insufficiency.

1 A pharmacokinetic study of nalidixic acid (NA) and metabolites was carried out in 23 patients with differing renal function so as to determine the influence of renal insufficiency on the excretion and biotransformation rate of this antibacterial agent. Plasma and urine concentration of NA and of its 7-hydroxy (HNA) and 7-carboxy (CNA) derivatives were measured after a single oral administration. 2 Renal insufficiency did not markedly affect the renal clearance of NA while it significantly decreased the elimination rate of HNA, a compound which largely excreted into the urine. 3 Interestingly, CNA which could never be detected in the plasma of patients with normal renal function appeared in that of patients with renal insufficiency. Plasma concentrations of CNA and creatinine were positively related, and the amount of urinary CNA increased with the renal impairment. 4 These results suggest that HNA can still be biotransformed into CNA by the impaired kidney. Since CNA cannot be easily excreted in the urine of patients with renal insufficiency it is hypothesized that this compound back diffuses into the plasma. 5 Finally, the study of the urinary concentrations of NA and metabolites shows that a standard NA dosage can be used, at least in patients with mild renal insufficiency.     

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.     

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。     

Enoxaparin-associated retroperitoneal bleeding in two patients with renal insufficiency

Two patients with chronic kidney disease experienced a major bleeding event, retroperitoneal hematoma, requiring a blood transfusion after the administration of enoxaparin. The first patient was a 61-year-old Caucasian woman with multiple comorbidities, including chronic kidney disease stage 4. She received subcutaneous enoxaparin 45 mg every 12 hours, along with antiplatelet agents. On the seventh day, she developed a large retroperitoneal hematoma and her hematocrit had decreased, requiring a transfusion of packed red blood cells. The second patient was a 74-year-old, obese Caucasian woman with multiple comorbidities, including chronic kidney disease stage 2-3 and atrial fibrillation. She was given enoxaparin 120 mg every 12 hours, along with warfarin and aspirin to prevent embolization. She developed a large retroperitoneal hematoma and died despite vigorous supportive care. Enoxaparin should be administered with great caution in patients with chronic kidney disease, especially if antiplatelet agents or other anticoagulants are administered concomitantly.     

Pharmacokinetics of ramipril in hypertensive patients with renal insufficiency

In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 25 hypertensive patients with various degrees of renal insufficiency given 5 mg ramipril p.o. for 14 days. Ramipril was rapidly absorbed and reached a peak concentration after 1-2 h. Cmax was greater in patients with severe renal insufficiency, which might indicate a reduced renal elimination rate, although, the rapid decline of the concentration-time curve for ramipril was almost independent of renal function. The mean initial apparent half-lives on Days 1 and 12, respectively, were 2.8 and 3.4 h (Group I: creatinine clearance 5-15 ml/min), 1.8 and 2.3 h (Group II: creatinine clearance 15-40 ml/min), and 1.9 and 1.9 h (Group III: creatinine clearance 40-80 ml/min). No accumulation was observed after multiple dosing. In contrast, the kinetics of its active acid metabolite ramiprilat was significantly influenced by renal function. The mean times to the peak plasma concentration were 5.7 h in Group I, 4.4 h in Group II and 3.8 h in Group III. The initial decline in plasma ramiprilat was dependent upon renal function; the mean initial apparent half-lives (Days 1 and 12, respectively) were 16.0 and 14.8 h (Group I), 10.1 and 9.5 h (Group II) and 10.6 and 8.0 h (Group III). Mean trough concentrations and absolute accumulation also increased with worsening renal function, and the renal clearance of ramiprilat was significantly correlated with the creatinine clearance. The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex.(ABSTRACT TRUNCATED AT 250 WORDS)     

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。     

卡托普利加重肾功能损害11例

卡托普利(Captopril,Cap)已广泛应用于高血压和充血性心衰的治疗,它对肾功能的保护作用也得到了肯定,但卡托普利的肾毒性不可忽视,现报告和分析卡托普利加重肾功能损害11例.     

Sulindac kinetics and effects on renal function and prostaglandin excretion in renal insufficiency

The purpose of this study was to evaluate the pharmacokinetics of sulindac, a purported "renal sparing" nonsteroidal anti-inflammatory drug, and its effects on renal function and prostaglandin excretion in patients with reduced glomerular filtration rate. Twelve female patients (glomerular filtration rate 37 +/- 4 mL/min) were treated with sulindac 200 mg bid for 11 days. Urinary PGE2, 6-keto-PGF1 alpha and serum thromboxane (TxB2) generation were measured by radioimmunoassay (RIA) following extraction on C-18 columns. Glomerular filtration rate and effective renal plasma flow were measured by 99TC-DPTA and 131I-para-aminohippuric acid clearance. In six patients serum and urine levels of sulindac and its metabolites were measured by high-pressure liquid chromatography (HPLC). Sulindac was rapidly absorbed and converted to sulindac sulfide with peak levels 2 hours after a single dose, but steady state levels were not reached prior to drug discontinuation. Sulindac sulfide AUC (0-5 hours micrograms min/mL) progressively increased from 382 to 3,030 on day 11. It did not appear in the urine. Baseline urinary PGE2 and 6-keto-PGF1 alpha excretion were 23.8 +/- 5.6 and 18.9 +/- 2.7 ng/hr respectively and were reduced by 68% and 47% by day 4 of therapy. TxB2 generation fell by 34% after one dose and by 67% by day 11. There was a significant increase in serum creatinine from 1.88 +/- 0.13 mg/dl before treatment to 2.16 +/- 0.15 mg/dL (P less than .05) after eleven days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of flurbiprofen on renal function in patients with moderate renal insufficiency.

1. Renal function was assessed in eight patients with chronic renal insufficiency following the administration of flurbiprofen 50 mg as a single dose and after chronic administration of 50 mg four times daily for 8 and 27 days. Diet and fluid intake were controlled. 2. Inulin and creatinine clearances and urinary excretion of sodium were measured at baseline and every 20 min for at least 3 h after dosing. The time of the mean peak concentration of (S)-flurbiprofen was used to guide the analysis of the clearances. Creatinine clearance, urinary excretion of sodium, and serum sodium and potassium were also assessed for 24 h after the dose and on a daily basis. Body weight and blood pressure were measured on a daily basis. 3. Decrements in inulin and creatinine clearances were small and reversible within 3 h of an oral dose of flurbiprofen. Comparison of baseline clearances for the three study periods (first dose and at 8 and 27 days of chronic dosing) revealed a lack of chronic effect on glomerular filtration rate. 4. In contrast, flurbiprofen caused a substantial (73 to 86%) and progressive decrease in the urinary excretion of sodium that reached a nadir within 4-5 h after drug administration. However, comparison of baseline values did not differ, indicating that balance conditions had been re-established. 5. Results of 24 h assessments were in agreement with the clearance study results. Reduced urinary excretion of sodium appeared to be limited to the first few days of flurbiprofen administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

心房颤动伴肾功能不全的危险因素研究

【摘要】目的分析心房颤动（AF）伴肾功能不全的危险因素。方法确诊为AF的住院患者529例,按AF是否合并肾功能不全分为2组,合并组303例,非合并组226例,比较2组相关临床资料,研究AF患者伴肾功能不全的可能危险因素。结果合并组的年龄、合并高血压、心功能不全及冠心病病史的比例高于非合并组（P＜0.05）,而2组性别、吸烟史、糖尿病、风湿性瓣膜病、甲亢、心肌病、特发性AF、左房扩大出现肾功能不全的发生率间差异无统计学意义。回归分析结果显示,年龄≥60岁、既往有高血压、冠心病及心功能不全是AF患者并发肾功能不全的危险因素。结论对老年性AF患者,加强其血压的管控、冠心病的防治及心功能的改善,对预防肾功能不全尤为重要     

The effect of famotidine on renal function in patients with renal insufficiency.

The effect of famotidine, a new histamine H2-receptor antagonist, on renal tubular creatinine secretion was evaluated in twelve patients with reduced renal function (creatinine clearance 10-60 ml min-1). Creatinine and inulin clearances were determined at baseline and for 4 h after a 10 mg intravenous dose of famotidine. Famotidine renal clearance exceeded inulin clearance by an average of 152%, indicating that renal tubular secretion of famotidine occurred. No significant changes in the clearances of creatinine or inulin, or the fractional clearance of creatinine were observed after famotidine administration. These data suggest that famotidine, unlike cimetidine, does not inhibit renal tubular secretion of creatinine. Thus, famotidine does not affect creatinine-dependent measurements of renal function and is unlikely to alter the renal elimination of basic drugs.     

Lead exposure and renal failure: Does renal insufficiency influence lead kinetics?

Blood and urine lead concentrations have been measured in 40 subjects with normal and impaired renal function. Derived renal lead clearance varied widely, but was not influenced by the degree of renal impairment. Lead, however, appeared to reduce its own clearance. These findings provide additional evidence of nephrotoxicity from sub-clinical lead exposure.     

Sex differences in diazepam protein binding in patients with renal insufficiency

Sex differences in the extent of binding of diazepam to plasma protein were assessed in a series of patients with renal insufficiency previously described by Kangas et al. Among identifiable independent variables, sex alone accounted for the greatest proportion of variability in percent unbound diazepam (r = 0.33), whereas age and serum creatinine accounted for practically none. The mean (+/- SE) percent unbound among females (10.8 +/- 2.8%) was larger (p less than 0.1) than among males (5.8 +/- 1.3%). Since only the unbound fraction of diazepam in plasma is available for pharmacologic activity, the intensity and duration of diazepam's clinical action in patients with renal insufficiency might differ between males and females.     

The effect of nifedipine GITS on renal function in hypertensive patients with renal insufficiency

Twelve hypertensive patients with moderately severe renal dysfunction were entered into a protocol to assess the blood pressure and renal effects of the sustained release calcium antagonist, nifedipine GITS (30-180 mg/d given once a day) administered for 5 weeks. Nifedipine GITS monotherapy effectively lowered blood pressure in 50% of the patients. Glomerular filtration rate and effective renal plasma flow were increased 18% and 20%, respectively. The filtration fraction and urinary protein excretion remained unchanged. Changes that were observed in renal function were independent of the blood pressure responses of the patients; there was no correlation between the systemic and renal effect of nifedipine GITS monotherapy. Patients who had a poor systemic blood pressure response exhibited an increase in glomerular filtration rate (+11%) but had a decrease in effective renal plasma flow (-6%); patients who achieved a goal blood pressure response showed increases in both glomerular filtration rate (+35%) and effective renal plasma flow (+40%). These results show that nifedipine GITS monotherapy has the potential to improve renal function abnormalities that are encountered in hypertensive patients with renal disease; the improvement in renal function may be independent of their effect on systemic blood pressure.