Effect of drugs on oro-caecal transit time assessed by the lactulose/breath hydrogen method

Summary The comparative actions of two benzamides; the one metoclopramide, having and the other, BRL 20627, lacking dopamine receptor antagonist properties have been investigated on orocaecal transit time (OCTT) using the lactulose/breath hydrogen method. In addition, the action of codeine, propantheline and domperidone on OCTT has been assessed. Similar quantitative reductions in apparent OCTT were found with metoclopramide and BRL 20627 thus, metoclopramide 20 mg orally and 10 mg i.v. brought about 32.5% and 42% reductions in OCTT. Similar reductions were also found using 20 mg BRL 20627 orally and 10 mg i.v. (31 and 26% respectively). In addition 20 mg domperidone orally was found to cause a 10% reduction. Codeine orally and propantheline i.m. brought about increases in the assessed transit time.     

红霉素治疗新生儿胃肠道功能紊乱的疗效观察

目的 探讨不同剂量红霉素治疗新生儿胃肠道功能紊乱的临床效果.方法 选取收治的新生儿胃肠道功能紊乱患儿129例,按照治疗方法分为大剂量组、小剂量组与对照组各43例,大剂量组及小剂量组分别予红霉素10mg＆#183; kg-1＆#183;次-1、3mg＆#183;kg-1＆#183;次-1治疗,对照组予等量氯化钠溶液.比较3组患儿肠内营养时间、肠外营养时间、肝功能损害及住院时间.结果 3组肠内营养时间中半量时间、3/4量时间、全量时间及肠外营养时间最短的为大剂量组,其次为小剂量组,最后为对照组,3组间差异有统计学意义（P＜0.05）.大剂量组的肝功能损害与小剂量组比较差异无统计学意义,但明显低于对照组,差异有统计学意义（P＜0.05）;住院时间最短的为大剂量红霉素组,其次为小剂量红霉素组及对照组,3组间差异有统计学意义（P＜0.05）.结论 采用不同剂量红霉素治疗新生儿胃肠道功能紊乱,可明显缓解患者胃肠道功能紊乱,且大剂量红霉素效果明显优于小剂量.     

Effect of codeine on oro-cecal transit time in Chinese healthy volunteers in comparison with Caucasian subjects

Objectives: To evaluate the effect of codeine on oro-cecal transit time (OCTT) in Chinese subjects. Methods: OCTT was measured with the hydrogen breath test in 12 Chinese healthy volunteers on two occasions: after placebo and after a single oral dose of codeine 50 mg. Codeine and its metabolites in urine were measured by HPLC. The Results of this study were compared with those previously obtained from Caucasian subjects. Results and conclusion: The mean OCTT increased significantly after a single oral dose of codeine 50 mg [2.6 (1.2) h] compared with placebo [1.9 (0.6) h] in the Chinese subjects (P = 0.05). The increase in OCTT after codeine was similar in the Caucasian [0.9 (0.8) h] and in the Chinese subjects [0.7 (0.9) h]. However, the Chinese subjects had a significantly longer OCTT after placebo [1.9 (0.6) h] compared with the Caucasian subjects [1.3 (0.6) h, P < 0.05], possibly due to different environmental factors. Received: 20 April 1998 / Accepted in revised form: 10 August 1998     

Effect of compression force on the crystal properties of erythromycin acistrate tablets

The crystal properties of compressed and powdered erythromycin acistrate tablets were studied by the X-ray powder diffraction (XRPD) method. Detailed analysis of X-ray powder diffraction line profiles was performed. Diffraction peak intensities and full width at half maximum (FWHM) values of the peaks corresponding to three different crystal lattice directions were determined. Crystallite size was calculated by Scherrer's equation using the data of integral breadth of the peaks. The preferred orientation of the crystallites is also discussed. According to the results, the crystallite size increased on the tablet surface after a small compression force (4 kN) in all crystal lattice directions studied. Even small compression forces caused recrystallization. With higher compression forces (8–18 kN) the crystallite size and the FWHM values remained rather constant. After the compression force of 18 kN the peaks in different crystal lattice directions behaved differently. In the lattice directions of diffraction maxima 2 and 3, the effect was the same with the small (4 kN) and the high compression force (22 kN). Further recrystallization occurred with 22 kN. However, in the crystal lattice direction of diffraction maximum 1 at the compression force of 8 kN the crystallite broke and crystallinity decreased. These were not seen in the powdered tablet samples. It could be concluded that the effect of compression force on the crystal properties of erythromycin acistrate tablets was seen on the tablet surface but not in the powdered tablets. Compression force also affected the preferred orientation of crystallites on the tablet surface and especially in the lattice direction of diffraction maximum 3. This was not seen in the powdered tablets.     

小剂量红霉素治疗早产儿胃肠道功能紊乱

目的:评价小剂量红霉素治疗早产儿胃肠道功能紊乱的疗效。方法:将诊断明确的129例患儿随机分为治疗组65例,对照组64例,对照组予常规对症支持治疗,治疗组在常规处理基础上加用小剂量红霉素3~5mg/(kg·d)缓慢静脉滴注,1次/d,连用4~10d。结果:治疗组呕吐症状、胃潴留缓解以及奶量增加和体重增长有效率分别是83.1%、81.5%、73.8%、78.5%,均明显高于对照组(P<0.05),且无明显副作用。结论:小剂量红霉素治疗早产儿胃肠道功能紊乱安全有效,具有一定的临床价值。     

Effect of dehydration on the disposition kinetics of erythromycin in rabbits.

The effect of water deprivation on the physiologic, biochemical, and disposition parameters of erythromycin was investigated in rabbits. The packed cell volume, plasma glucose, and total lipid concentration increased significantly in dehydration. The pharmacokinetic parameters of erythromycin after intravenous administration also changed, suggesting a need for monitoring toxicity of erythromycin in the water-deprived population.     

Single-dose fasting bioequivalence assessment of erythromycin stearate tablets in man

The bioequivalence of film-coated erythromycin stearate tablets produced by five different manufacturers was evaluated in a balanced incomplete block design involving the five formulations given to 30 fasted subjects over a 3-week study period. Serum levels of erythromycin activity were determined microbiologically. Statistical analysis of variance was performed on the observed bioavailability parameters: maximum serum concentration C_max, time to maximum serum concentration (t_max), and area under the serum concentrationtime curve (AUC). There was no statistical difference between formulations for the t_max parameter. Formulation differences were found, however, based on the analysis of variance of the C_max and AUC parameters. Two products, although not significantly different from one another, showed significantly greater C_max and AUC values than the other three products.This work was supported in part by FDA Contract 74-3004.     

Effect of multiple-dose erythromycin on everolimus pharmacokinetics

Objective We sought to quantify the influence of the CYP3A inhibitor erythromycin on the pharmacokinetics of everolimus, a CYP3A substrate.Methods This was a two-period, single-sequence, crossover study in 16 healthy subjects. In period 1, subjects received the reference treatment of a single 2-mg dose of everolimus. In period 2, they received the test treatment of erythromycin 500 mg three times daily for a total of 9 days and a single 2-mg dose of everolimus coadministered on the fifth day of erythromycin therapy. The test/reference ratio and 90% confidence interval (CI) were derived for everolimus C _max and AUC.Results During erythromycin coadministration, everolimus C _max increased 2.0-fold (90% CI, 1.8–2.3) from 20±5 ng/ml to 40±10 ng/ml. Everolimus AUC increased 4.4-fold (90% CI, 3.5–5.4) from 116±37 ng h/ml to 524±225 ng h/ml. Everolimus half-life was prolonged by 39% from 32±6 h to 44±6 h. Erythromycin predose concentrations were not changed after single-dose administration of everolimus. Conclusion Multiple-dose erythromycin increased single-dose everolimus blood levels by an average 4.4-fold (range, 2.0–12.6). During erythromycin treatment, a compensatory everolimus dose reduction should be made guided by everolimus therapeutic drug monitoring.This study was financed by Novartis Pharmaceuticals.     

肠易激综合征治疗前后氢呼气试验参数及胃肠激素分泌水平的变化研究

目的 探究肠易激综合征(IBS)患者治疗前后氢呼气试验参数及胃肠激素分泌水平的变化情况.方法 采用氢呼气试验测定正常对照组及IBS患者口盲传输时间(OTCC)及产生H2浓度,同时利用放射免疫法检测正常对照组及IBS患者血浆中胃动素(MTL)、血管活性肠肽(VIP)、胆囊收缩素(CCK)和生长抑素(SS)的含量.结果 治疗前腹泻组患者OCTT显著低于对照组和便秘组,且便秘组OCTT显著高于对照组(P＜0.05),治疗前IBS患者H2浓度和SIBO阳性率均显著高于对照组(P＜0.05),治疗后H2浓度和SIBO阳性率显著降低,差异有统计学意义(P＜ 0.05).治疗前腹泻组患者血浆中MTL和CCK明显高于对照组和便秘组,治疗后腹泻组患者MTL和CCK水平较治疗前显著降低,而便秘组较治疗前显著升高(P＜0.05);而治疗前IBS患者血浆中VIP和SS明显高于对照组,治疗后IBS患者VIP和SS水平较治疗前显著降低,差异有统计学意义(P＜0.05).结论 氢呼气试验参数和胃肠激素分泌水平改变与IBS发病过程密切相关.     

Effect of erythromycin and itraconazole on the pharmacokinetics of intravenous lignocaine

Objective: We have studied the possible interaction of erythromycin and itraconazole, both inhibitors of cytochrome P450 3A4 isoenzyme (CYP3A4), with intravenous lignocaine in nine healthy volunteers using a randomized cross-over study design. Methods: The subjects were given oral placebo, erythromycin (500 mg three times a day) or itraconazole (200 mg once a day) for 4 days. Intravenous lignocaine 1.5 mg · kg⁻¹ was given with an infusion for 60 min on the fourth day of pretreatment with placebo, erythromycin or itraconazole. Timed plasma samples were collected until 11 h. The concentrations of lignocaine and its metabolite monoethylglycinexylidide (MEGX) were measured by gas chromatography. Results: The area under the lignocaine concentration-time curve was similar during all three phases but erythromycin significantly increased the elimination half-life of lignocaine from 2.5 to 2.9 (0.7) h compared with placebo. Following itraconazole administration, t_1/2 was 2.6 h. The values for plasma clearance and volume of distribution at steady state were similar during all the phases. Compared with placebo and itraconazole, erythromycin significantly increased MEGX peak concentrations by approximately 40% and AUC_(0–11 h) by 45–60%. Conclusion: The plasma decay of lignocaine administered intravenously is virtually unaffected by the concomitant administration of erythromycin and itraconazole. However, erythromycin increases the concentrations of MEGX, which indicates that erythromycin either increases the relative amount of lignocaine metabolized via N-de-ethylation or decreases the further metabolism of MEGX. Further studies are necessary to elucidate the clinical significance of the erythromycin-induced elevated concentrations of MEGX during prolonged intravenous infusions of lignocaine. Received: 8 January 1998 / Accepted in revised form: 8 June 1998     

琥乙红霉素胶囊处方工艺研究及溶出度测定

目的　琥乙红霉素胶囊处方筛选及溶出度测定。方法　通过正交试验筛选出胶囊剂的处方 ,采用硫酸比色法测定其溶出度。结果　最佳处方为 5 0 g·L-1的 CMC- Na、5 g交联 PVP、0 .5 g十二烷基硫酸钠、0 .5 g蔗糖酯 ;胶囊 30 min时溶出度大于 80 %。结论　组方合理 ,制备工艺简便易行 ,溶出度可控     

有机氮源对红霉素发酵影响的具体分析

红色糖多孢菌的摇瓶培养基中使用不同有机氮源时红霉素的效价明显不同。通过对不同有机氮源所含营养成分的逐步回归分析,我们得到有机氮源中的苏氨酸为影响红霉素效价的主要因子。最后向对照培养基中添加苏氨酸,则使红霉素的效价比对照培养基提高了22.85%。     

小剂量红霉素治疗小儿功能性消化不良33例疗效观察

目的探讨小剂量红霉素治疗小儿功能性消化不良的治疗效果。方法将66例功能性消化不良患儿随机分成治疗组33例和对照组33例,两组均在常规处理的同时,对照组予吗叮林每次0.3mg/kg,每日3次口服;治疗组给予红霉素口服,剂量为10mg/(kg.d),3次/日,两组疗程均为5天,对两组疗效进行评价。结果:治疗组总有效率90.90%;对照组总有效率60.60%,两组疗效差异有统计学意义,P<0.01。结论小剂量红霉素治疗小儿功能性消化不良具有良好的治疗效果。     

Behaviour and transit of tamsulosin Oral Controlled Absorption System in the gastrointestinal tract

ABSTRACT

Objective: To assess the in vivo behaviour, gastric emptying time and gastrointestinal transit of the new tablet formulation of tamsulosin which uses the Oral Controlled Absorption System (OCAS) technology and to relate gastrointestinal transit parameters to the profile of the plasma concentration time curve.

Research design and methods: After breakfast, 8 healthy male subjects received a single tamsulosin OCAS 0.4?mg tablet labelled with 4MBq technetium-99m. Scintigraphic images were taken immediately after dosing, every 15?min until 15?h post-dose and at 24?h post-dose. Blood samples for pharmacokinetic analysis were taken up to 24?h after dosing. Safety was assessed by physical examinations, vital signs, laboratory safety evaluations and adverse events monitoring.

Results: A mean C_max of 7.84 ± 2.54?ng/mL was achieved after 5.13 ± 1.25?h (t_max). The mean gastric emptying time for the tablet was 4.1 ± 2.5?h. Mean transit time through the small intestine was 3.6 ± 2.9?h; the mean colonic arrival time 7.7 ± 2.9?h post-dose and the mean release time (spread of the technetium-99m label from the tablet core) 12.3 ± 1.7?h post-dose. In all cases where release of the radiolabelled tablet was observed, this occurred within the colon. Variations in gastric residence, small intestinal transit or colonic residence did not apparently influence release time or site.

Conclusions: The results suggest that tamsulosin is released from the OCAS formulation throughout the entire gastrointestinal tract, including the colon, indicating consistent and continued 24‐h drug release. This correlates with a more consistent pharmacokinetic profile.     

Studies on the intravenous pharmacokinetics in rabbit and in vitro protein binding of two new salts of erythromycin: erythromycin maltobionate and erythromycin fumarate.

Pharmacokinetics in rabbits following intravenous administration and in vitro protein binding were studied for two new salts of erythromycin (erythromycin maltobionate and erythromycin fumarate). Serum erythromycin levels following intravenous injection were described by two compartment model kinetics, and values for the distribution volume of the central compartment, the peripheral compartment and overall distribution volume were calculated. The elimination half-lives of erythromycins in serum were 83 min, 168 min, and 103 min for erythromycin maltobionate, erythromycin fumarate, and erythromycin lactobionate (reference standard), respectively. The erythromycin salts were highly (c. 90 per cent) protein bound, but the binding was found to be reversible. Differences in the pharmacokinetic parameters after administration of equivalent doses of the salts, indicate possible variation in efficacies of different salts.     

红霉素发酵液大孔树脂法脱色过程研究

考察大孔树脂对红霉素发酵液的脱色作用，详细研究了工艺条件对树脂脱色能力的影响。实验结果表明，在室温下。以1BV／h的流速进行吸附时，D293树脂对红霉素发酵液具有良好的脱色效果。处理量为10BV时，脱色率为68％；并对树脂再生条件作了研究。     

Effect of loperamide on jejunal electrolyte and water transport,prostaglandin E 2-induced secretion and intestinal transit time in man

Summary Jejunal perfusion was performed in 12 healthy volunteers to evaluate the dose dependent effects of loperamide on intestinal absorption, stimulated secretion and transit.In 6 volunteers intestinal perfusion of the jejunal segment with isotonic NaCl solution was followed by addition of loperamide in increasing doses (2–8 mg·l^–1). The volunteers were pretreated with 1 mg·l^–1 prostaglandin E2 (PgE2) in the perfusate before addition of 4 mg·l^–1 loperamide. Phenolsulphonphtalein (PSP) boluses (2 ml) were given to measure mean transit time (MTT).Loperamide 2 mg·l^–1 converted the minor secretion after perfusion with the standard solution (water –1.45 ml·min^–1, Na –0.09 and Cl –0.04 mmol·min^–1) to absorption (water 0.93 ml·min^–1, Na 0.23, Cl 0.25 mmol·min^–1) within 15 min. Higher doses of loperamide did not increase absorption.The addition of PgE2 induced net secretion of water (–4.48 ml·min^–1) and electrolytes (Na –0.57, Cl –0.51 mmol·min^–1). Loperamide 4 mg·l^–1 significantly diminished the PgE2-induced net secretion by approximately 50%.Loperamide dose dependently increased the MTT from 6 (2 mg·l^–1) to 13.3 min (8 mg·l^–1). MTT was still delayed 60 min after a wash out period (10.5 min).It is concluded that loperamide had a dual effect or intestinal activities stimulating absorption and prolonging intestinal transit time with rising doses.     

红霉素发酵过程次级代谢的混沌现象研究

采用参数相关分析的发酵过程优化理论对红霉素发酵过程进行研究 ,发现红霉素产生菌发酵初期的菌体生长状态对整个发酵过程及最后的生产水平都会产生较大的影响 ,即所谓红霉素发酵次级代谢的混沌现象 ,通过对红霉素早期的有效控制 ,取得了显著的效果。     

红霉素发酵培养基优化研究

对红霉素发酵培养基进行了优化，选用A粉和B粉代替原工艺中的淀粉及部分葡萄糖和豆饼粉。采用正交试验设计方法。确定最佳发酵培养基配方，并考察了中间补料方案。经10吨发酵罐连续8批验证，平均发酵效价提高6．11％，产品质量全部合格。原材料消耗成本可降低20％以上。     

正常结肠运动与血中胃泌素、生长抑素含量的初步研究

目的探讨结肠运动与胃泌素、生长激素的关系。方法 90例正常人 ,其中男性 5 2例 ,女性 38例 ,分青年组 34例 ,中年组 33例 ,老年 2 3例。运用结肠运输实验观察各年龄组结肠运输情况 ,采用放免法测定其餐前后血中GAS及SS的浓度。结果 (1)结肠运输试验 :青、中、老年组结肠运动力由强减弱 ,青、中年组 4 8小时内结肠运动力明显高于老年组 (P <0 0 5 )。男女组间结肠运输试验差异无显著意义 (P >0 0 5 )。 (2 )正常人空腹血清GAS、血浆SS的浓度 :分别为 5 1 0 0± 2 1 92 pg/ml、17 72± 11 6 8pg/ml,餐后血GAS、SS :分别为 10 2 15± 4 9 15 pg/ml、37 30± 30 0 7pg/ml。 (3)餐后 1小时各组血中GAS、SS浓度 ,青年组分别为 10 5 4 7± 5 6 4 2pg/ml、32 6 8± 17 2 5 pg/ml;中年组分别为 :10 4 38± 38 6 7pg/ml、33 6 5± 2 0 98pg/ml;老年组分别为 94 13± 5 1 87pg/ml、6 1 70±30 80 pg/ml;老年组餐前后血中SS与青、中年组相比差异有显著意义 (P >0 0 5 )。 (4)空腹与餐后比较 :青、中、老年组餐后GAS、SS均明显高于餐前 (P <0 0 5 )。 (5 )、2 4、4 8、72小时 80 %TT组间SS浓度递升。结论 (1)本研究结肠运输试验结果符合 72小时 80 %TT标准。 (2 )正常人血中GAS、SS :空腹分别为 5 1 0