Pharmacokinetics of Nitrazepam in Saliva and Serum after a Single Oral Dose

Abstract The pharmacokinetics of nitrazepam in saliva and serum was studied in 12 healthy volunteers after a single administration of a 5 mg nitrazepam tablet. The binding of nitrazepam to plasma proteins was determined 4 hours after the administration by ultracentrifugation. The analysis of nitrazepam concentrations was performed by ⁶³Ni-EC-GLC. The pharmacokinetic parameters were evaluated manually or by AUTOAN-program in serum, and manually in saliva. The concentrations of nitrazepam in serum and saliva correlated significantly (r=0.472, P<0.001, n=97). The ratio saliva: serum was, however, time dependent. The protein free fraction in serum was significantly higher (P<0.01) than the salivary concentration at the same time (4 hours after administration). The peak concentrations in serum and saliva were 40.7 and 1.9 ng/ml (P<0.001) and the times to reach the peak maximum 2.4 and 2.5 hours, respectively (difference not significant). The mean half-life of nitrazepam in serum was 30.5 hrs and in saliva 39.9 hrs, the difference being significant at P<0.05. The distribution phase parameters, poorly described before, were calculated. The clinical value of nitrazepam analysis in saliva seems to be negligible.     

研究左氧氟沙星0.5g治疗泌尿道细菌感染的临床疗效

目的:观察左氧氟沙星0.5g剂型治疗泌尿道细菌感染的临床疗效。方法:对62例细菌性泌尿道感染患者给予左氧氟沙星静脉点滴5天,之后口服左氧氟沙星10天,静脉点滴和口服的剂量均为0.5g,1日1次,1个疗程15天,研究治疗前及治疗后患者临床症状体征和实验室检查的变化,应用敏感度高的序贯设计检验方法。结果:实验至30例时,实验线已超过上边界线,结果为有效。经过1个疗程15天的治疗,临床症状体征和实验室检查较应用本药前改善75%(P<0.01)。结论:左氧氟沙星0.5g剂型在泌尿道细菌感染治疗中疗效确切。     

儿童再发性尿路感染的预防

尿路感染(UTI)是儿童时期最常见的感染性疾病之一。由于儿童的自身发育特点,其患病率较成人高。1/3 ~ 1/2 的患病儿童可能会再发至少1 次。1 年内反复发作3 次或6 个月内发作2 次尿路感染称再发性尿路感染(RUTI)。15% ~ 65% 的RUTI 患儿可能出现肾皮质永久瘢痕。长期并发症包括高血压、慢性肾功能不全,甚至导致终末期肾病。为预防RUTI,减少其造成持续性肾脏损害和瘢痕化,临床上提出了多种预防策略。笔者根据近些年相关文献资料,就儿童RUTI 的预防措施作一综述。     

单剂量加替沙星口服在Beagle犬体内药代动力学研究

目的探讨加替沙星口服后在Beagle犬体内药代动力学。方法将18只Beagle犬分为3组,分别灌服34,17,8.5mg/kg加替沙星,于给药后0.5,1,2,4,6,8,12,24,36,48,60h取血,以高效液相色谱法测定血药浓度,用3P97程序分析。结果高、中、低剂量组动物吸收相半衰期(t1/2ka)分别为(0.82±0.96),(0.78±0.77),(1.33±0.43)h,消除相半衰期(t1/2ke)分别为(7.33±1.79),(6.32±3.28),(5.34±2.60)h,达峰时间(tmax)分别为(6.32±2.32),(3.95±2.18),(5.77±1.62)h,峰浓度(Cmax)分别为(6.31±2.66),(2.67±0.64),(0.64±0.30)mg/mL。药时曲线下面积(AUC0→60)分别为(110.86±43.76),(41.93±5.58),(8.58±2.70)μg·h/mL。结论加替沙星口服易吸收,血药浓度高,代谢慢,临床使用方便。     

Pharmacokinetics and Dose Regimen of Oral Theophylline in Children

Abstract: The pharmacokinetics of theophylline after oral administration in tablet (Oxyphyllin®) or solution (Teovent®) form was determined in 22 children 0.6–16 years of age. Four of these children also received intravenous theophylline. The absorption of theophylline both from the tablets and from the solution was rapid (mean half-time 14.3 and 16.1 min., respectively) and almost complete. The youngest children (2–8 years) given tablets had a significantly shorter half-time of elimination and a higher total plasma clearance than children aged 9–16 years. Adverse effects during treatment with the oral solution were studied in another 19 children. Medication was stopped by the parents of two children because of the unpleasant taste. Gastrointestinal disturbances were frequent but not serious enough to cause discontinuation of treatment. Simulations based on obtained pharmacokinetic data showed that in the average child below nine years of age oral theophylline, 6–8 mg/kg three times daily, would give plasma levels between 10 and 20 μg/ml (55–110 μmol/l) for about 60–70% of the day. A dose of 6 mg/kg four times daily would achieve such concentrations during almost 24 hrs of the day. In the average child aged 9–16 years a reduced dose of about 5–6 mg/kg three times daily would suffice to produce plasma levels of 10–20 μg/ml owing to the slower elimination of the drug in this age group. Individual titration of the dose is necessary for optimal treatment with theophylline in all age groups.     

Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats

Memantine is a non‐competitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist used to treat Alzheimer's disease. We investigated memantine pharmacokinetics after oral, IV and patch administration in rats, and compared memantine pharmacokinetics after multiple‐ or single‐dose oral and transdermal administration. Venous blood was collected at preset intervals in single‐ and multiple‐dose studies. Non‐compartmental pharmacokinetics was analysed for all formulations. The oral, IV and patch memantine doses were 10 mg/kg, 2 mg/kg and 8.21 ± 0.89 mg/kg, respectively. The maximum plasma concentration was lower and the half‐life longer after patch administration than oral and IV administration. Memantine bioavailability was 41 and 63% for oral and patch administration, respectively. Steady state was achieved around 24 hr for oral and patch administration. The mean AUC increased after oral or patch administration from single to multiple dose. The memantine patch formulation displayed a longer duration of action and lower peak plasma concentration. However, drug exposure was similar to the oral formulation at each dose. Additionally, the memantine patch formulation displayed a smaller interindividual variability and lower accumulation than the oral formulation.     

综合护理措施对小儿泌尿系统感染治疗依从性的影响

目的研究综合护理措施对小儿泌尿系统感染治疗依从性的影响。方法选取2011年1月—2012年6月来本院住院治疗的64例泌尿系统感染患儿,将患儿随机分成对照组和试验组,每组32例。对照组给予常规护理,试验组采用综合护理,比较两组患儿治疗依从性及对护理人员的满意度。结果试验组服药依从性、门诊随访依从性、护理满意度均高于对照组,差异有统计学意义（P〈0.05）。结论综合护理措施能提高泌尿系统感染患儿的治疗依从性,减少家属负担。     

单剂量口服阿德福韦酯片人体药动学研究

目的:研究单剂量口服阿德福韦酯片在健康人体中的药动学。方法:采用随机、开放、三交叉设计试验,12名健康志愿者随机分为3组,在3周期里单次空腹口服阿德福韦酯片5、10、30mg,用高效液相色谱-质谱串联法测定血浆药物浓度,计算药动学参数。结果:单剂量口服阿德福韦酯片5、10、30mg后阿德福韦的主要药动学参数Cmax分别为(11·4±3·7)、(25·4±8·2)、(76·3±23·0)ng·mL-1,tmax分别为(1·69±1·41)、(0·90±0·56)、(0·94±0·50)h,AUC0～t分别为(102·7±51·7)、(235·0±82·3)、(715·4±267·6)ng·h·mL-1,AUC0～∞分别为(168·7±30·7)、(266·2±83·7)、(741·5±273·9)ng·h·mL-1。结论:阿德福韦酯吸收迅速,Cmax、AUC与剂量呈正相关。健康志愿者单剂量口服阿德福韦酯片5～30mg较安全。     

悉能对呼吸道感染患者的药代动力学

目的：研究静脉输注悉能（硫酸依替米星）在呼吸道感染患者体内的药代动力学。方法：采用微生物法测定了１０例呼吸道感染患者静脉滴注２００ｍｇ悉能的血、尿及痰中药物浓度,并进行药代动力学研究。结果与结论：该药在呼吸道感染患者体内最高血药浓度为１４．７４μｇ／ｍｌ,１２ｈ仍维持在０．２９μｇ／ｍｌ。经ＰＫＢＰ－Ｎ１药代动力学程序拟合符合二室开放动力学模型,其参数为Ｔ１／２α＝０．２５７ｈ,Ｔ１／２β＝２．２２ｈ,Ｖｃ＝３４．３２Ｌ,Ｋ２１＝２．１４ｈ～（－１）,Ｋｌ２＝０．４８ｈ～（－１）,Ｋ１０＝０．３９ｈ～（－１）。１２ｈ肾排泄累积百分比为２１．３７％,Ｋｅ＝０．０２７ｈ～（－１）,Ｋ＝０．４３１ｈ～（－１）。痰中药物浓度在滴注结束后２ｈ达到最高值,即 ２．０９μｇ／ｍｌ。     

Effect of Carbamazepine on the Single Oral Dose Pharmacokinetics of Alprazolam

The effect of carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics of alprazolam was examined in a double-blind, randomized crossover study with two phases. Seven healthy male subjects took carbamazepine 300 mg/day or matched placebo orally for 10 days, and on the 8th day they took a single oral 0.8 mg dose of alprazolam. Blood samples were taken and psychomotor function was assessed by the Digit Symbol Substitution Test, Visual Analog Scale, and UKU Side Effect Rating Scale up to 48 h after alprazolam dosing. Carbamazepine significantly (p < .01 to .001) decreased the plasma alprazolam concentrations during the elimination phase. Carbamazepine significantly (p < .001) increased the apparent oral clearance (0.90 ± 0.21 vs. 2.13 ± 0.54 ml/min/kg) and shortened the elimination half-life (17.1 ± 4.9 vs. 7.7 ± 1.7 h), with no significant effect on the peak plasma concentration (11.7 ± 1.5 vs. 13.0 ± 3.5 ng/ml). The majority of psychomotor function parameters during the carbamazepine treatment were not significantly different from those during the placebo treatment, probably because of the sedative effect of carbamazepine itself. The present study suggests that carbamazepine decreases plasma concentration of alprazolam by inducing its metabolism. It also supports the previous studies, suggesting that alprazolam is metabolized predominantly by CYP3A4.     

小儿反复呼吸道感染的免疫治疗临床研究

目的探讨免疫调节剂匹多莫德口服液治疗小儿反复呼吸道感染的临床疗效和免疫价值。方法将本院儿科收治的86例反复呼吸道感染患儿随机分为观察组和对照组各43例,对照组给予青霉素及利巴韦林注射液常规治疗,观察组在对照组常规治疗的基础上,同时给予匹多莫德口服液。观察二组临床疗效和不良反应,并测定IgA、IgG、IgM、CD3+、CD4+、CD8+、CD4+/CD8+及NK细胞等免疫指标的水平治疗前后变化值。结果治疗后观察组总有效率为90.7%,显著高于对照组48.8%(P<0.05);治疗前,两组患者IgA、IgG、IgM、CD3+、CD4+、CD8+、CD4+/CD8+及NK细胞等免疫指标无显著性差异(P>0.05);治疗后,观察组各项免疫指标检测值较治疗前显著升高(P<0.05),对照组各项免疫指标较治疗前无显著性变化(P>0.05);两组患儿均未出现严重不良反应。结论匹多莫德口服液能有效地改善小儿反复呼吸道感染患者免疫系统功能,提高治疗疗效,且临床无明显不良反应,可推广使用。     

Dose-Dependent Pharmacokinetics of a New Oral Cephalosporin,Cefixime, in the Dog

Cefixime (CL 284,635; FK 027) is a new third-generation oral cephalosporin. To study dose-dependent pharmacokinetics of cefixime in dogs, two balanced four-way crossover studies were conducted. In the first study, oral doses of 50, 100, and 200 mg/kg and an intravenous dose of 50 mg/kg cefixime were administered. In the second study, oral doses of 6.25, 12.5, and 25 mg/kg and an intravenous dose of 12.5 mg/kg cefixime were administered to the same dogs. A period of 1 month separated the two studies. When the two intravenous doses were compared (i.e., 12.5 and 50 mg/kg), a twofold increase in clearance and volume of distribution was observed after the higher dose. The oral systemic bioavailability in the dose range 6.25–50 mg/kg was 55%. It decreased to 44% at 100 mg/kg and 27% at 200 mg/kg. The average peak serum concentrations ranged from 15.8 µg/ml at 6.25 mg/kg to 119 µg/ml at 200 mg/kg. Within this concentration range, the fraction of free drug in serum (unbound to proteins) increased from 7 to 25%. This concentration-dependent protein binding was primarily responsible for changes in total clearance, volume of distribution, and bioavailability of the drug in dogs.     

高效液相色谱法测定人血浆中卡托普利和人体药动学的研究

目的　建立简便的测定人血浆中卡托普利血药浓度的高效液相色谱法 ,研究卡托普利在健康人体中的药动学参数。方法　以对溴苯乙酰基溴为紫外衍生化试剂 ,采用高效液相色谱紫外检测法测定 18名健康志愿受试者口服单剂量卡托普利受试制剂和参比制剂 ( 5 0mg)后血药浓度。结果　卡托普利的血药浓度标准曲线的线性范围为 2 5～ 12 0 0ng·mL- 1 ,其最低定量限为 2 5ng·mL- 1 ,日内及日间RSD均小于 8%。应用所建立的血药浓度检测方法测定 18名健康志愿受试者口服单剂量卡托普利受试制剂和参比制剂 ( 5 0mg)后血药浓度 ,并计算药动学参数。结果表明口服受试制剂或参比制剂后的tmax分别为( 0 6 4± 0 18)h和 ( 0 82± 0 4 1)h ;Cmax分别为 ( 6 0 0 2± 194 3)ng·mL- 1 和 ( 5 82 7± 175 3)ng·mL- 1 ;AUC0→ 8h分别为 ( 14 4 8 5± 4 83 7)ng·h·mL- 1 和 ( 1389 9± 392 5 )ng·h·mL- 1 ;AUC0→∞ 分别为 ( 186 9 4± 70 1 6 )ng·h·mL- 1 和 ( 1781 8± 6 15 5 )ng·h·mL- 1 。结论　本方法操作便捷 ,灵敏度高 ,为血药浓度监测及药代动力学研究提供了方法学基础     

Metabolism of Beclamide after a Single Oral Dose in Man: Quantitative Studies

A simple reverse phase HPLC assay is described for the determination of the anticonvulsant compound, beclamide and its 3- and 4-hydroxyphenyl metabolites in urine. Following oral administration of 1 g beclamide to a panel of healthy volunteers, less than 0.4% of the dose was excreted unchanged in the 24-h urine and unconjugated 3- and 4-hydroxyphenyl metabolites were not detected. Based on examination of the urine after incubation with β-glucuronidase and aryl sulphatase, it was found that these hydroxyl metabolites were excreted as both glucuronide and sulphate conjugates. For each metabolite the glucuronide was the major excretory product (approximately 10: 1). The 24-h excretion of the combined conjugated metabolites was 7% (for the 3-hydroxy metabolite) and 24% (for the 4-hydroxy metabolite) of the dose. Approximately 22% of the administered dose of beclamide was excreted as hippuric acid. In view of the simplicity of assay, beclamide may be a useful tool substance with which to examine factors influencing the xenobiotic metabolic pathways of benzene ring hydroxylation and glucuronide and sulphate conjugation in man.     

单次口服硫辛酸胶囊在中国健康志愿者体内的药物动力学研究

目的:研究硫辛酸胶囊在中国健康人体内的药物动力学。方法:22名健康志愿者单剂量口服硫辛酸胶囊200 mg,用HPLC-MS法测定硫辛酸血浓度,并拟合药动学参数。结果:主要的药动学参数Ka为(0.109±0.117)min~(-1),t_(1/2)为(24.42±9.51)min,t_(max)为(16.59±4.47)min,C_(max)为(1489.93±358.65)ng·ml~(-1),AUC_(0-1)为(59558.64±18456.17)ng·min·ml~(-1),MRT_(0-t)为(46.46±14.73)min,Vc/F为(129.09±59.59)L,Cls/F为(3646.83±1110.76)ml·min~(-1)。结论:健康志愿者口服硫辛酸胶囊后的体内过程呈线性动力学特征,符合一级消除过程。     

糖尿病合并尿路感染120临床治疗分析

目的探索糖尿病合并尿路感染患者的有效治疗方法。方法回归性分析120例糖尿病合并尿路感染患者的临床资料,比较采用二甲双胍联合比格列酮控制血糖及抗感染治疗其他方法控制血糖及抗感染治疗对糖尿病尿路感染的治疗效果。结果 120例患者中43例采用二甲双胍联合比格列酮及抗感染治疗,治愈40例,好转2例,无效1例,治愈率93%,好转率5%,有效率98%。77例采用其他方法控制血糖及抗感染治疗,治愈54,好转19例,无效4例,治愈率70%,好转率25%,有效率95%。结论采用二甲双胍联合比格列酮及抗感染治疗,更有助于糖尿病尿路感染的治疗。     

氟康唑治疗泌尿系统真菌感染

目的：观察氟康唑对泌尿系统真菌感染的治疗效果.方法：泌尿系统真菌感染15例,用氟康唑200 mg,静脉滴注,bid,疗程一般为7～10 d,临床症状基本控制后改为氟康唑100 mg,bid,po,维持治疗15～20 d.结果：总有效率为93.3%,真菌清除率为86.7%,不良反应发生率为20.0%,无严重不良反应.结论：氟康唑为治疗泌尿系统真菌感染安全而有效的药物.     

泌尿道感染抗菌药物的应用

泌尿道感染是常见病,涉及人群广泛,临床表现以尿路刺激征为主,可合并全身感染中毒症状或菌血症,细菌培养阳性是确诊依据,抗菌治疗方案因感染部位、菌种、病程长短、有无复杂因素、社区或医院获得,有无尿管等不同,正确的预防措施是防止感染的重要手段.