阿奇霉素微球干混悬剂的研制及其药动学

按不同处方制备阿奇霉素-乙基纤维素(EC)微球并进行质量评价。再将微球制成干混悬剂,考察其在12名健康志愿者体内的药动学情况。结果表明,微球的优化处方为药物-EC重量比2∶1,EC浓度50mg/ml,水油相比15∶1,用其制成的干混悬剂口感好、无苦味。自制干混悬剂和参比干混悬剂的药-时曲线形状相似,AUC0～96h分别为(7.61±1.31)和(7.45±1.66)μg·h·ml-1。     

阿奇霉素片的人体药物动力学及相对生物利用度

研究了20名健康志愿者单剂量口服两种阿奇霉素片后的血药浓度经时过程,以及两者的生物等效性评价。以微生物法测定血清中阿奇霉素的浓度,供试制剂的Cmax为580.75±156.62μg/L,T     

阿奇霉素分散片的人体药物动力学和生物等效性研究

20名健康男性志愿者交叉口服两种国产阿奇霉素分散片的受试制剂和参比制剂500mg,以HPLC-MS法测定血浆中阿奇霉素的浓度,研究人体药物动力学参数和生物等效性。采用C_8柱,流动相为甲醇-0．02mol／L乙酸铵溶液(70:30), 受试制剂和参比制剂的C_(max)分别为(472．14±216．37)和(432．96±131．80)ng／ml t_(1／2)分别为(68．63±12．93)和(70．63± 15．61)h;T_(max)分别为(2．18±0．89)和(2．25±0．84)h; AUC_(o→144h)分别为(4268．52±1252．89)和(4370．32±807．82)ng·h·ml~(-1)。经方差分析和双单侧t检验,说明两片剂具有生物等效性,受试制剂的相对生物利用度为(97．1±22．7)％。     

Single- and Multiple-dose Mibefradil Pharmacokinetics in Normal and Hypertensive Subjects

Mibefradil is a single-enantiomer calcium antagonist belonging to a new class, the tetralol derivatives. The recommended doses for treatment of hypertension and chronic stable angina pectoris are 50 or 100 mg. Mibefradil is metabolized via parallel pathways of esterase-catalysed hydrolysis and cytochrome P450 3A4-mediated oxidation. Mibefradil also inhibits cytochrome P450 3A4 and consequently inhibits its own metabolism, a property illustrated by three studies performed early in the drug's development. After single intravenous doses of 2.5 to 80 mg to healthy male subjects, pharmacokinetics are linear. At the representative 40 mg intravenous dose mean pharmacokinetic parameters were clearance 241 ± 76 mL min^?1, terminal exponential half-life 15.0h and volume of distribution at steady state 213 L. After single oral doses of 10 to 320 mg, reduced first-pass metabolism occurs with increasing dose. This effect is accompanied by increasing absolute bioavailability as the dose is increased. In an oral multiple-dose study of healthy male volunteers mibefradil doses of 100, 150 or 250 mg (from tablets) were administered once daily for 28 days. Reduction of the first-pass effect was noted, although the data suggested that a maximum was reached for doses of 150 mg or more. In a study of the effect of hypertension on mibefradil pharmacokinetics, 12 patients received oral mibefradil once daily at doses of 50, 100, 150, or 200 mg in 100 mL orange juice for 8 days. Steady state was reached within 3 days and accumulation generally ranged from three- to sevenfold. Single-dose non-linearity was observed in the first-pass effect, although for multiple dosing oral clearance values were dose-independent and lower than for single doses. After multiple dosing at the recommended dosage of 50 and 100 mg once daily, oral clearance of mibefradil stabilizes to approximately the same value for both doses. Hence, the single-dose non-linearity has little clinical relevance but demonstrates the self-inhibition of metabolism seen with mibefradil. Studies so far suggest that self-inhibition of its oxidative metabolic pathway leads to a low clearance and long half-life, enabling once-daily dosing and conferring low intra- and inter-patient variability in pharmacokinetics.     

Single- vs Multiple-Dose Pharmacokinetics of Clozapine in Psychiatric Patients

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.     

阿奇霉素胶囊人体生物利用度研究

目的采用HPLC-MS法测定志愿者口服阿奇霉素胶囊(250 mg)后的血药浓度,对受试制剂与参比制剂的生物等效性进行评价。方法20名健康志愿者交叉口服受试制剂或参比制剂250 mg。计算主要药动学参数及相对生物利用度,以判断生物等效性。结果在5~1200 ng.ml-1范围内阿奇霉素峰面积与内标峰面积的比值与阿奇霉素的浓度之间呈良好线性关系,最低定量限为5 ng.ml-1。受试制剂和参比制剂的t1/2分别为(45.89±8.69)h(、51.04±10.31)h,tmax分别为(2.0±0.7)h(、2.2±0.7)h,cmax分别为(532.55±182.65)ng.ml-1(、466.00±180.21)ng.ml-1。以AUC0-τ计算的受试胶囊的相对生物利用度为(107.4±25.5)%。两制剂的药动学主要参数无显著性差异。结论2种制剂具有生物等效性。     

阿奇霉素治疗小儿支原体肺炎的疗效观察

目的探讨阿奇霉素治疗支原体肺炎的临床疗效。方法选择临床诊断为支原体肺炎的患儿160例,随机分为两组,阿奇霉素（治疗）组、红霉素（对照）组各80例,治疗组按10mg／（kg·d）给予注射用阿奇霉素静脉滴注,对照组给予红霉素15—30mg／（kg·d）静脉滴注。结果治疗组和对照组总有效率分别为97．5％和90．0％,两组比较差异有统计学意义（P〈0．05）,阿奇霉素出现的胃肠道反应、局部疼痛等不良反应明显低于红霉素（P〈0．05）。结论阿奇霉素治疗小儿支原体肺炎明显优于红霉素,是一种安全、有效的药物,值得临床上推广使用。     

阿奇霉素干混悬剂的人体药动学及生物等效性研究

目的:评价2种阿奇霉素干混悬剂的生物等效性。方法:20名男性健康志愿者随机交叉口服受试制剂或参比制剂10袋(含阿奇霉素1.0g)后,采用反相高效液相色谱法测定血浆中的药物浓度,并计算有关药动学参数,通过方差分析和双单侧t检验和1～2α置信区间法进行生物等效性评价。结果:受试制剂与参比制剂中阿奇霉素的Cmax分别为(29.651±5.600)、(29.256±6.382)μg·mL-1,tmax分别为(2.25±0.444)、(2.400±0.503)h,t1/2分别为(37.910±10.181)、(37.980±9.220)h,AUC0～120分别为(458.139±47.368)、(463.114±42.267)μg.h.mL-1,AUC0～∞分别为(519.217±57.262)、(522.980±48.267)μg.h.mL-1。受试制剂相对于参比制剂的生物利用度为(99.5±8.9)%。结论:2种制剂生物等效。     

阿奇霉素在中国健康人体血浆中的药动学研究

目的:研究阿奇霉素在健康中国人体中的血浆药动学,为临床用药提供参考。方法:10名健康志愿者单剂量口服阿奇霉素500 mg后,HPLC法测定血浆药物浓度。采用F检验结合AIC法判别房室模型,DAS药动学程序计算药动学参数。结果:最佳房室模型为二室模型(W_i=1/C~2,AIC=-7.48),主要的药动学参数:α为(0.29±0.13)h~(-1),B为(0.02±0.003)h~(-1),Ka为(0.72±0.22)h~(-1),t_(1/2β)为(38.93±7.74)h,t_(max)为(2.60±0.49)h,C_(max)为(434.74±47.65)μg·L~(-1),AUC_(0-144)和AUC_(0-∞)分别为(12179.42±3001.11)μg·h·L~(-1)和(13338.35±3062.56)μg·h·L~(-1)。结论:阿奇霉素片在中国健康人体中的血浆药动学参数与国内外文献报道基本一致。     

阿奇霉素分散片人体药动学及生物等效性研究

目的研究阿奇霉素分散片健康人体的药动学与生物等效性。方法20名男性健康志愿者随机交叉口服阿奇霉素分散片受试制剂和参比制剂各500mg,采用高效液相色谱-质谱法（LC-MS）测定血药浓度。以DAS2.0软件计算其药动学参数,考察其生物等效性。结果受试制剂和参比制剂阿奇霉素AUC0-168分别为（8.98±1.74）μg·h·mL^-1和（8.75±1.60）μg·h·mL^-1,Cmax分别为（0.81±0.14）μg·mL^-1和（0.80±0.14）μg·mL^-1,t^1/2分别为（48.16±11.10）h和（51.1±7.60）h,Tmax分别为（1.80±0.86）h和（1.82±0.92）h,受试制剂相对于参比制剂的生物利用度为（103.4±20.2）%。结论阿奇霉素分散片受试制剂和参比制剂具有生物等效性。     

阿奇霉素治疗小儿支原体肺炎40例

目的：评价阿奇霉素治疗小儿支原体肺炎的临床疗效和安全性.方法：支原体肺炎患儿80例,随机分为治疗组和对照组各40例,进行单盲对照试验,治疗组给予注射用阿奇霉素10 mg•kg 1•d 1,用0.9%氯化钠注射液稀释为1～2 mg•mL 1,分2次,q 12 h,静脉滴注,每次滴注时间不少于60 min,3～7 d后改为阿奇霉素口服；对照组用红霉素15～30 mg•kg 1•d 1,用10%葡萄糖注射液或0.9%氯化钠注射液稀释为1 mg•mL 1,静脉滴注.两组均以治疗7～10 d为1个疗程.结果：治疗组和对照组的3 d显效率分别为72.5%,37.5%；7 d治愈率分别为50.0%,23.7%；10 d治愈率分别为95.0%,77.5%；不良反应发生率分别为10.0%,30.0%,并且对照组2例因严重不良反应而停药.结论：与红霉素相比,阿奇霉素治疗小儿支原体肺炎具有疗效高、不良反应发生率低、起效快等优点     

阿奇霉素肠溶片的人体药动学与生物等效性研究

目的建立测定阿奇霉素血药浓度的微生物法,并评价阿奇霉素肠溶片与普通阿奇霉素片的生物等效性。方法采用微生物法,测定24例健康受试者单剂量交叉口服受试制剂阿奇霉素肠溶片或参比制剂普通阿奇霉素片500 mg后不同时间点的血浆药物浓度,计算药动学参数和相对生物利用度,评价两制剂的生物等效性。结果阿奇霉素肠溶片与普通阿奇霉素片AUC0→144 h分别为(21.021±4.053)和(20.597±3.850)mg.h-1.L-1,Cmax分别为(0.583±0.073)和(0.603±0.061)mg.L-1,tmax分别为(3.900±0.800)和(3.000±0.700)h,t1/2分别为(29.799±1.935)和(28.850±1.598)h。两制剂主要药动学参数差异无显著性。结论该实验所建立的方法简便快捷,两制剂具有生物等效性,但受试制剂阿奇霉素肠溶片在人体内的吸收速度较参比制剂阿奇霉素普通片慢。     

Pharmacokinetics and Pharmacodynamics of Pentazocine in Children

Pharmacokinetics and ventilatory effects of a single intravenous dose of 0.5 mg/kg of pentazocine were studied in ten children aged 4 to 8 years after ophthalmic surgery. Elimination half-life (mean ± S.D.) was 3.0×1.5 hr and clearance 21.8×5.9 ml/min./kg. The values for V_c, V_ss and V_β were 0.73×0.21, 4.0×1.2 and 5.3×2.1 1/kg, respectively. The pharmacokinetic parameters were similar to those of adults. After administration of pentazocine decrease in ventilatory rate and oxygen saturation and increase in end-tidal carbon dioxide were relatively fast and steep. Oxygen saturation of four patients decreased below 90% and in one patient the decrease did not recover instantly and additional oxygen was given for 2 min. No patient needed assisted ventilation. Only clinically insignificant changes in heart rate and mean arterial pressure were observed. The duration of analgesia was 164 × 59 min. No serious side-effects appeared.     

阿奇霉素对大鼠灌服华法林的药效学和药动学的影响

目的：研究抗生索阿奇霉素对大鼠灌服华法林的药效学指标凝血酶原时间（PT）和国际标准化比值（INR）以及药动学指标血药浓度的影响。方法：将SD大鼠随机分成两组：单用华法林组（A组）和华法林＋阿奇霉素合用组（B组）,每组大鼠灌胃给予华法林0．2mg·kg^-1,每日1次,连续613,其中B组大鼠在第6日最后1次灌胃给予华法林后立即腹腔注射阿奇霉素80mg·kg^-1,且开始计时,分别于0．25、0．5、1．5、2．5、3．5、5、7、10、13小时采血,测定PT,计算INR。并建立HPLC法,测定华法林血药浓度。结果：从5小时开始,B组大鼠的胛值较A组显著增大（P〈0．05）,INR值最高可达7．5;B组大鼠的华法林药动学参数咒。较A组显著延长（P〈0．01）,其他药动学参数无显著性差异;两组大鼠的INR-C曲线都呈逆时针走向,且B组的逆时针效应更甚。结论：阿奇霉素与华法林合用可发生药效学和药动学相互作用,增强华法林的抗凝作用,增加用药者的出血风险,故临床上两药合用时应密切监测用药者的INR值,避免严重不良反应的发生。     

阿奇霉素在中国健康人体血浆中的药动学研究

OBJECTIVE To study the pharmacokinetics of azithromycin tablet in Chinese healthy volunteers.METHODS 10 healthy volunteers were given a single oral dose of 500mg azithromycin tablet.The plasma concentrations of azithromycin were determined by HPLC-UV.The     

阿奇霉素在中国健康人体血浆中的药动学研究

目的研究阿奇霉素在健康中国人体中的血浆药动学,为临床用药提供参考。方法10名健康志愿者单剂量口服阿奇霉素500mg后,高效液相色谱-紫外检测法测定血浆药物浓度。采用F检验结合AIC法判别房室模型,DAS药动学程序计算药动学参数。结果最佳房室模型为二室模型(Wi=1/C2,AICmin=-7.4821),主要的药动学参数:α为(0.29±0.13)h-1,β为(0.02±0.003)h-1,Ka为(0.72±0.22)h-1,t1/2β为(38.93±7.74)h,tmax为(2.60±0.49)h,cmax为(434.74±47.65)μg.L-1,AUC0～144和AUC0～∞分别为(12179.42±3001.11)μg.h.L-1和(13338.35±3062.56)μg.h.L-1。结论阿奇霉素片在中国健康人体中的血浆药动学参数与国内外文献报道基本一致。     

Population Pharmacokinetics of an Extended-Release Formulation of Exenatide Following Single- and Multiple-Dose Administration

Exenatide is a glucagon-like peptide-1 receptor agonist with both immediate- and extended-release (ER) formulations that are approved for the treatment of type 2 diabetes mellitus. Long-term exposure from the ER formulation is achieved through slow peptide release from a degradable microsphere formulation. The goal of this analysis was to develop a pharmacokinetic model for the ER formulation following single and once-weekly multiple-dose administration. Pharmacokinetic data were collected from two clinical trials—one that evaluated single-dose administration of 2.5, 5, 7, and 10 mg of ER exenatide and a second that included weekly administration of 0.8 and 2 mg for 15 weeks. A population pharmacokinetic model, describing 1586 exenatide concentrations from 64 patients, was developed in the nonlinear mixed-effects modeling software program NONMEM. Pharmacokinetics of the ER formulation was described by a two-compartment model with linear and nonlinear elimination. The complex absorption profile was quantified using three simultaneous processes: a first-order process characterizing a rapid initial release and two series of transit compartments to describe the second (～3 weeks postinjection) and third phases of drug release (～7 weeks postinjection). Estimation of the combined single- and multiple-dose data adequately described the rise to steady-state (～8–10 weeks) and decline to undetectable concentrations that occurred about 10 weeks after treatment cessation. Thus, a population-based pharmacokinetic model was developed that provides a platform for future pharmacodynamic analyses with the ER formulation of exenatide.     

阿奇霉素治疗小儿肺炎的疗效观察

目的分析观察阿奇霉素治疗小儿肺炎的疗效。方法收集120例肺炎患儿,将其随机分为2组,分别设为对照组(n=60)与实验组(n=60)。其中,对照组,给予红霉素治疗,而实验组,给予阿奇霉素治疗,分析比较2组患儿的临床疗效。结果实验组,痊愈29例,有效27例,无效4例,总有效率为93.3%(56/60),对照组,痊愈18例,有效29例,无效13例,总有效率为78.3%(47/60),比较2组患儿的治疗结果,差异显著,有统计学意义(P<0.05)。结论小儿肺炎,给予阿奇霉素治疗,效果显著,有推广价值。     

Malnutrition and Pharmacokinetics of Penicillin in Ethiopian Children

Abstract: Penicillin was given to 104 children with different nutritional status, normal, underweight, marasmus and kwashiorkor. Penicillin was given either intravenously, intramuscularly or orally and the plasma concentration was followed at regular times after administration. There was a significantly decreased plasma clearance of penicillin in all malnourished groups compared to the normal weight-for-age group. The half-lives of penicillin were, however, not significantly different between the nutritional groups. This was explained by the fact that also the volume of distribution was decreased in the malnourished group with a net result that the half-life was unchanged. The bioavailability was decreased if penicillin was given to non-fasting individuals. The greatest difference between fasting and non-fasting was seen in the severely malnourished children with marasmus and kwashiorkor. Therefore, it is advised that, if penicillin is given orally to very sick and undernourished children, the dose should be increased and preferably be given in the fasting state.     

阿奇霉素治疗小儿肺炎疗效观察

目的:观察和分析阿奇霉素治疗小儿肺炎的疗效。方法:选取某院收治的小儿肺炎患者80例为对象进行研究,将其利用计算机随机分组为对照组与观察组,各40例。在常规治疗的基础上,对照组采用红霉素静脉滴注治疗,观察组采用阿奇霉素静脉滴注治疗,分析比较两组患者病症消失时间以及临床疗效。结果:观察组咳嗽消失时间为(5.06±1.23)d、鸣音消失时间为(2.35±1.12)d,而对照组咳嗽消失时间为(6.43±1.87)d、鸣音消失时间为(10.18±2.15)d,观察组与对照组相比差异显著(P0.05),具有统计学意义。观察组的治疗有效率为92.5%(37/40),明显好于对照组77.5%(31/40),且组间对比P0.05,具有统计学意义。结论:阿奇霉素治疗小儿肺炎后能够获得显著的临床疗效,且患者各种临床症状快速消失,还能降低不良反应的发生率,具有较高的安全性以及可靠性,值得应用于临床推广。