阿奇霉素不同给药方案治疗儿童急性鼻窦炎的疗效观察

目的观察阿奇霉素不同给药方案治疗儿童急性鼻窦炎的临床疗效。方法 60例急性鼻窦炎患儿,随机分为观察组和对照组,各30例。观察组患儿口服阿奇霉素,给药3 d,停4 d;对照组患儿连续口服阿奇霉素。观察比较两组患儿治疗7、14 d后的临床疗效以及患儿不良反应(腹泻、恶心、腹痛、食欲差)发生情况。结果观察组患儿治疗7、14 d后的临床总有效率分别为86.67%、93.33%,对照组患儿治疗7、14 d后的临床总有效率分别为90.00%、93.33%,两组比较差异无统计学意义(P>0.05)。观察组治疗7、14 d后不良反应发生率分别为13.33%、16.67%,低于对照组的16.67%、30.00%,但差异无统计学意义(P>0.05)。结论阿奇霉素治疗儿童急性鼻窦炎,服3 d停4 d的服药法与1次/d服法的疗效相当,间歇的服药方法更容易为患儿和家长接受,且副作用较小。这种简便的服法值得临床推广应用。     

Once daily clarithromycin extended-release vs twice-daily amoxicillin/clavulanate in patients with acute bacterial sinusitis: a randomized,investigator-blinded study

ABSTRACT

Objective: To compare the efficacy and tolerability of clarithromycin extended-release (ER) to amoxicillin/clavulanate in patients diagnosed with acute bacterial sinusitis.

Research design and methods: In a controlled, multicenter, investigator-blinded study, 437 ambulatory patients at least 12?years old with signs/symptoms and radiographic findings of acute sinusitis were randomized to receive clarithromycin ER 1000?mg once daily or amoxicillin/clavulanate 875?mg/125?mg twice daily for 14?days.

Main outcome measures: Clinical and bacteriological response rates were determined at a test-of-cure visit, which was conducted up to 10?days following the completion of treatment. Radiological response was assessed at a follow-up visit.

Results: The clinical cure rate in clinically evaluable patients was 98% (184/188) in the clarithromycin ER group and 97% (179/185) in the amoxicillin/clavulanate group (95% CI for the difference in rates [–2.4%, 4.7%]). Clinical cure was sustained at the follow-up visit (96% for each treatment group). The pathogen eradication rates were 94% (61/65) in the clarithromycin ER group and 98% (61/62) in the amoxicillin/clavulanate group (95% CI for difference in rates [–12.0%, 2.9%]). The radiological success rate was 94% (172/183) in both the clarithromycin ER and amoxicillin/clavulanate groups (95% CI for difference in rates [–4.9%, 4.9%]). Symptomatic improvement or relief was observed as early as 2?days–5?days after the initiation of study drug, with a statistically significantly higher resolution rate of sinus pressure (?p = 0.027) and improvement/resolution rate of nasal congestion (?p = 0.035) during treatment with clarithromycin ER. The resolution/improvement rate at the test-of-cure visit for each treatment group was ≥ 94% for the primary acute sinusitis signs/symptoms, with a statistically significantly higher resolution/improvement rate of purulent nasal discharge with clarithromycin ER (?p = 0.010). Both study drugs had a positive and rapid impact on quality of life. Patients reported a high level of satisfaction and probability of using either study antibiotic again, and health care resource use was low, with slightly fewer sinusitis-related physician and outpatient visits required by patients in the clarithromycin ER group (?p = 0.055). The treatment groups were comparable with respect to incidence of drug-related adverse events.

Conclusion: In this multinational population of patients with acute bacterial sinusitis, clarithromycin ER was comparable, and for selected measures superior, to amoxicillin/clavulanate based on clinical, bacteriological, and radiological responses as well as quality of life measures, satisfaction with antibiotic therapy, and health care resource utilization.     

Pharmacokinetics of extended-release and immediate-release formulations of galantamine at steady state in healthy volunteers

ABSTRACT

Objective: To assess the steady-state galantamine (GAL) bioavailability of the extended-release 24‐mg qd capsule (GAL‐ER) with and without food and to evaluate the relative bioavailability of GAL‐ER with the immediate-release 12‐mg bid tablet (GAL‐IR) at steady state.

Methods: This was a single-center, open-label, randomized, 3-way crossover study in 24 healthy volunteers (12 males and 12 females) aged 18 to 45 years. After 7 days of GAL‐ER 8?mg qd each morning and 7 days of GAL‐ER 16?mg qd each morning, subjects received the following treatments in randomized, crossover order (7 days each): GAL‐ER 24?mg qd each morning (fasted before Day 7 morning dose), GAL‐ER 24?mg qd each morning (fed before Day 7 morning dose), and GAL‐IR 12?mg bid (fasted before Day 7). Pharmacokinetic parameters of GAL at steady state were determined after morning intake on Day 7 of each treatment week. Safety evaluations included adverse event (AE) reporting, physical examination, clinical laboratory tests, vital signs, and electrocardiography.

Results: The treatment ratios of area under the plasma concentration-time curve of GAL from time 0–24?h post-dosing (AUC_{24 h}), peak plasma concentration (C_max), and pre-dose plasma concentration (C_min) for GAL‐ER fed/fasting were 105%, 112%, and 103%, respectively. The treatment ratios and 90% confidence intervals for all above mentioned pharmacokinetic parameters demonstrated bioequivalence (with the range of 80-125%), indicating that food had no effect on GAL‐ER bioavailability. As anticipated, GAL‐ER (fasting) had mean AUC_{24 h} similar to GAL‐IR (fasting), with lower C_max (63 ng/mL vs 84 ng/mL) and longer time to reach C_max (4.4?h vs 1.2?h). The treatment ratios and 90% confidence intervals for both AUC_{24 h} and C_min demonstrated bioequivalence (within the range of 80-125%). The treatment ratio for C_max was 75.7%, indicating a 24% lower C_max for GAL‐ER than for GAL‐IR. In this study, GAL‐ER was safe and well tolerated with or without food and was comparable to the GAL‐IR formulation.

Conclusion: Food had no effect on the GAL bioavailability of GAL‐ER at steady state. GAL‐ER was bioequivalent to GAL‐IR with respect to AUC_{24 h} and C_min.     

欧龙马滴剂联合阿奇霉素治疗儿童慢性鼻窦炎的疗效观察

目的探讨欧龙马滴剂联合阿奇霉素治疗儿童慢性鼻窦炎的临床疗效。方法选取2013年7月—2014年6月昆山市第一人民医院收治的慢性鼻窦炎患儿131例,随机分为对照组(65例)和治疗组(66例)。对照组口服阿奇霉素颗粒5 mg/kg,1次/d,同时使用鼻用激素,1次/d。10 d为1个疗程,第1~6天用药,第7~10天停用。治疗组在对照组的基础上联合应用欧龙马滴剂,1个疗程为10 d,第1~5天,50滴/次,第6~10天,25滴/次,3次/d。两组均连续治疗9个疗程。观察两组的临床疗效,同时比较两组治疗前后鼻部症状、相关症状、睡眠障碍、情感结局、症状体征评分的变化。结果治疗后,对照组和治疗组的总有效率分别为87.69%、96.97%,两组总有效率比较差异有统计学意义(P0.05)。治疗后,两组患者鼻部症状、相关症状、睡眠障碍、情感结局、症状体征评分均较治疗前显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组各观察指标的降低程度优于对照组,两组比较差异具有统计学意义(P0.05)。结论欧龙马滴剂联合阿奇霉素治疗儿童慢性鼻窦炎具有较好的临床疗效,能明显改善患儿的总体症状体征,改善鼻腔症状,具有一定的临床推广应用价值。     

Pharmacokinetics of quinine in African patients with acute falciparum malaria.

The pharmacokinetics of quinine were studied in six Nigerian patients during acute uncomplicated falciparum malaria and convalescent periods. An oral dose of 10 mg/kg quinine dihydrochloride administered 8hourly for 7 days gave parasite and fever clearance times of 36.0 ± 16.6 h and 18.0 ± 6.4 h, respectively. From the individual quinine plasma profiles the mean plasma concentration of quinine at the time of parasite clearance was estimated as 4.5 ± 1.1 g/ml. Plasma quinine levels during malaria rose rapidly reaching a peak around the second and third days and declining thereafter as patients improved clinically. In acute malaria plasma quinine levels were more than two-fold higher than in convalescence; the mean AUC(0-12) in malaria was 37.9 ± 14.7 g.h/ml compared to 17.9 ± 8.5g.h/ml in convalescence. The apparent oral clearance (CL/F) and volume of distribution (Vd/F) duri ng the acute phase of the malaria (1.9 ± 0.7 ml/min/kg and 1.8 ± 0.9 l/kg, respectively) were significantly lower than in convalescence (4.5 ± 2.1 ml/min/kg and 4.2 ± 3.2 l/kg). The present data suggest that malaria parasites in African patients are still very sensitive to quinine and that the current dosage of quinine is effective for the treatment of acute falciparum malaria in African patients without augmenting therapy with any other drug such as tetracycline or sulphadoxine-pyrimethamine. It also confirms that malaria significantly alters the pharmacokinetics of quinine in humans.     

阿奇霉素干混悬剂 颗粒剂和胶囊的人体药代动力学研究

目的使用高效液相色谱-质谱(HPLC-MS)联用法测定人血浆中阿奇霉素的浓度,并研究阿奇霉素干混悬剂、颗粒剂和胶囊在健康人体内的药代动力学情况。方法 20名健康男性志愿者单剂量口服500mg阿奇霉素后,采集不同时间点血样测定血药浓度。结果阿奇霉素的线性范围为2.71～1084μg/L,日内和日间相对标准偏差(RSD)均<5.0%。阿奇霉素干混悬剂主要药代动力学参数为:Cmax:(453±130)μg/L;tmax:(2.3±0.9)h;t1/2:(48±6)h;平均驻留时间(MRT):(53±8)h;曲线下面积(AUC)0-t:(4694±903)μg·h-·1L-1;AUC0-∞:(5118±919)μg·h-1·L-1。结论 3种剂型阿奇霉素的药代动力学参数的差异无统计学意义。     

咪康唑鼻窦内灌注联合鼻内镜下手术治疗非侵袭性真菌性鼻窦炎的效果观察

目的探讨咪康唑鼻窦内灌注联合鼻内镜下手术治疗非侵袭性真菌性鼻窦炎的效果。方法将本院2011年12月～2012年12月收治的132例非侵袭性真菌性鼻窦炎患者随机分为对照组和观察组,每组各66例。对照组患者实施常规的鼻内镜下手术治疗,观察组患者实施咪康唑鼻窦内灌注联合鼻内镜下手术治疗,观察两组患者的总有效率、术后愈合时间、术后6个月内的复发情况。结果对照组患者总有效率为81．82％,观察组患者总有效率为96．97％,差异有统计学意义（P〈0．05）。对照组患者术后平均愈合时间（40．2±5．2）d,观察组患者术后平均愈合时间（26．3±3．6）d,差异有统计学意义（P〈0．05）。对照组患者术后6个月内复发20例,观察组患者术后6个月内复发5例,差异有统计学意义（P〈0．05）。结论咪康唑鼻窦内灌注联合鼻内镜下手术治疗非侵袭性真菌性鼻窦炎效果显著,术后伤口愈合快,复发率低,值得临床推广。     

Pharmacokinetics of promazine: I. Disposition in patients with acute viral hepatitis B

Concentrations of promazine in plasma, plasma water, red blood cells, and urine were measured after oral administration of the drug to six patients during and after apparent recovery from the acute phase of viral hepatitis B. None of the promazine pharmacokinetic parameters were significantly different during and after the acute phase; these parameters included clearance, free drug clearance, metabolic clearance, volume of distribution, distribution and elimination half-life values, plasma protein binding, and per cent excreted in the urine. During the acute period of the illness, SGOP, SGPT, alkaline phosphatase, and total bilirubin were increased in all patients; they returned to within or near the upper limits or normal after recovery. Despite the unchanged promazine disposition, four out of six patients had more severe promazine side-effects, such as sedation, postural hypotension, and dizziness during the acute phase of the illness. This study suggests that promazine disposition was not significantly altered as a consequence of viral hepatitis. However, the pharmacodynamic effects of promazine were changed significantly. Care must be taken with patients who are taking promazine during the acute phase of viral hepatitis B.     

Pharmacokinetics and dose proportionality of extended-release metformin following administration of 1000, 1500, 2000 and 2500 mg in healthy volunteers

The pharmacokinetics and dose-exposure relationship of an extended-release formulation of metformin (ER-metformin) was investigated in a randomized, single-dose, four-period crossover study in 24 healthy male volunteers. During each study period, subjects received a randomly assigned dose containing 1000, 1500, 2000 or 2500 mg metformin. Blood samples were drawn 0-72 h after dosing for pharmacokinetic and dose-proportionality assessment. Although several pairwise comparisons between dose groups were significant (p<0.05) with respect to dose-normalized C(max), AUC(0-72 h), and AUC( infinity ), the magnitude of the difference across the dose range was <20% for AUC(0-72 h) and AUC( infinity ), and was < or = 30% for C(max). The results indicate a consistent and predictable increase in metformin exposure with an extended-release formulation of metformin over 1000 to 2500 mg.     

鼻内镜手术前后慢性鼻窦炎患者鼻黏膜形态及功能的变化

目的观察鼻内镜手术前后慢性鼻窦炎患者鼻黏膜形态及功能的变化。方法选择本院2013年1～5月慢性鼻窦炎患者40例作为研究组,均行鼻内镜手术治疗,治疗前后均进行糖精试验及鼻黏膜光镜检查,观察治疗前后鼻黏膜形态变化情况,选择同期健康体检者40例进行对照研究。结果研究组术前糖精试验时间明显长于对照组（P〈0．05）,术后糖精试验实验时间与对照组比较,差异无统计学意义（P〉0．05）;光镜检查结果显示术后研究组患者炎性细胞浸润、黏膜细胞水肿、黏膜息肉、病理性腺体增生较术前明显减少（P〈0．05）,且除病理性腺体外,其他项目与对照组差异无统计学意义（P〉0．05）。结论慢性鼻窦炎患者鼻黏膜的结构和纤毛的清除功能受到损害。鼻内镜手术后3个月左右鼻黏膜结构和功能可基本恢复正常,但病理性腺体的恢复较慢。     

青藤碱电致孔给药的药动学及在关节腔中浓度的研究

目的比较电致孔与电加热条件下热敷给药时青藤碱在兔血液中的药动学及其在关节腔液中的浓度。方法在兔关节处分别进行电致孔和电加热热敷给药,给药后利用微透析技术收集关节腔透析液,同时通过耳缘静脉采血。串联质谱法测定血液及关节腔透析液中青藤碱浓度。DAS软件处理分析血药浓度数据,t检验分析关节腔透析液数据。结果电致孔给药组的AUC 0^∞为(3 915.0±537.7)ng·min·mL-1,是电加热给药组的2倍;Cmax为(29.3±4.9)ng·mL-1,是电加热给药组的2.5倍;tmax为(30.8±6.4)min比电加热给药组缩短20 min。电致孔给药时青藤碱在关节腔中的浓度是电加热给药的1.6∞为(3 915.0±537.7)ng·min·mL-1,是电加热给药组的2倍;Cmax为(29.3±4.9)ng·mL-1,是电加热给药组的2.5倍;tmax为(30.8±6.4)min比电加热给药组缩短20 min。电致孔给药时青藤碱在关节腔中的浓度是电加热给药的1.6⁶.9倍。结论电致孔与电加热给药相比增加了青藤碱入血的量,提高了青藤碱生物利用度,同时能让更多的青藤碱分布于关节腔局部。     

鼻炎宁联合莫西沙星治疗急性鼻窦炎疗效及对WBC和CRP影响

目的 探讨鼻炎宁联合莫西沙星治疗急性鼻窦炎疗效及对WBC和CRP影响.方法 将急性鼻窦炎患者80例随机分为研究组与对照组,各40例;研究组采用鼻炎宁联合莫西沙星治疗,对照组仅采用莫西沙星治疗;两组患者治疗疗程均为2周.结果 两组治疗2周总有效率对比差异有统计学意义(P＜0.05);两组治疗2周鼻塞、头痛、流涕积分较治疗前降低,差异均有统计学意义(均P＜ 0.05);研究组治疗2周鼻塞、头痛、流涕积分低于对照组,差异均有统计学意义(均P＜ 0.05);两组治疗2周WBC和CRP水平较治疗前降低,且差异均有统计学意义(均P＜0.05);研究组治疗2周WBC和CRP水平低于对照组,差异均有统计学意义(均P＜0.05);两组用药2周期间未发生严重药物不良反应.结论 鼻炎宁联合莫西沙星治疗急性鼻窦炎患者疗效明显,且可降低患者WBC和CRP水平,具有重要研究意义.     

Pharmacokinetics and pharmacodynamics of extended-release glipizide GITS compared with immediate-release glipizide in patients with type II diabetes mellitus

This study was designed to compare the pharmacokinetic and short-term pharmacodynamic profile of extended-release glipizide GITS (Glucotrol XL) given in a dosage of 20 mg once daily with that of immediate-release glipizide (Glucotrol) 10mg twice daily in patients with type II diabetes mellitus. In an open-label, randomized, two-way crossover study, each glipizide formulation was administered for 5 days. Serial blood samples were drawn at baseline and on the 5th day of each treatment phase for measurement of glipizide, glucose, insulin, and C-peptide concentrations. At steady state, the mean Cmax after immediate-release glipizide was significantly greater than after glipizide GITS, and the tmax was considerably shorter. Although the mean Cmin with glipizide GITS was about 80% higher than with immediate-release glipizide, the mean AUC0-24 was significantly lower. Despite the lower plasma concentrations with glipizide GITS in this short-term study, the two formulations had similar effects on serum concentrations of glucose, insulin, and C-peptide. The absence of a pronounced peak plasma concentration with the GITS formulation might confer advantages in terms of maintaining clinical effectiveness and reducing the potential to cause adverse effects.     

Pharmacokinetics and bioequivalence of two strontium ranelate formulations after single oral administration in healthy Chinese subjects

1. Pharmacokinetics of exogenous strontium (Sr) and bioequivalence of a new oral formulation of strontium ranelate compared with the brand-name drug in healthy Chinese subjects was evaluated.

2. A balanced, randomized, single-dose, two-treatment parallel study was conducted in 36 healthy Chinese subjects. Subjects were randomly allocated into two groups of 18 to receive a single oral dose of test formulation and reference formulation under a fasting state, respectively. Blood samples were collected at 19 designated time points up to 240-h post-dose. Serum concentrations of Sr were quantified by ICP-MS.

3. A total of 36 subjects were enrolled and completed the study. Nine mild adverse events in 6 subjects were reported. The C_max, AUC_0–72?h, AUC_0–t, and AUC_0–∞ of test and reference formulations shown as mean?±?SD were 6.97?±?1.78 and 6.78?±?1.80?µg/mL, 199?±?51 and 187?±?38?µg·h/mL, 303?±?89 and 278?±?54?µg·h/mL, and 337?±?109 and 305?±?60?µg·h/mL, respectively.

4. Two formulations were bioequivalent, and both were generally well tolerated.

     

Pharmacokinetics and pharmacodynamics of a slow-release formulation of diltiazem after the administration of a single and repeated doses to healthy volunteers

Diltiazem is a calcium antagonist used in angina pectoris and hypertension. There is little information concerning the slow-release (SR) formulation in the literature. The pharmacokinetics of diltiazem SR (120 mg) have been assessed over a 36 h period in healthy volunteers after single- (SD) and multiple-dose (MD) administrations. C_max, AUC_0–36, and AUC_0–∞ were significantly increased at steady state compared to the extrapolated SD values, suggesting accumulation of the drug. Renal and cardiovascular parameters have also been assessed at intervals of 3–6 h during baseline (B) and following single and multiple doses of diltiazem SR. Diuresis over a 24 h period was increased, but not significantly, by the administration of diltiazem SR i.e. 1782 ml (MD) and 1915 ml (SD), versus 1626 ml (B). Natriuresis and creatinine clearance were slightly decreased by diltiazem SR, compared to B values; this might be due to the relatively short period over which steady state was maintained (five days) and the effects of norepinephrine and angiotensine II on renal vasculature and the pharmacokinetics of diltiazem SR. No increase in the systolic blood pressure occurred after the administration of diltiazem SR; diastolic blood pressure and PR interval were decreased and increased respectively by diltiazem SR. These results do not appear to be clinically significant. Finally, no relation was found between the pharmacokinetics and pharmacodynamics of diltiazem. This may be attributed to the absence of clinically significant effects in healthy volunteers, the presence of active metabolites, the pharmacokinetics of the SR formulation and/or the accumulation of the drug at steady state.     

布洛芬缓释凝胶在急性牙周脓肿中的效果研究

目的：探讨布洛芬缓释凝胶在急性牙周脓肿中的效果,以为其治疗提供依据。方法：选取2009年1月～2010年1月于本院进行治疗的70例牙周脓肿患者为研究对象,将其随机分为观察组（布洛芬缓释凝胶组）35例和对照组（常规治疗组）35例,后将两组患者的治疗后2、4周龈沟出血指数及牙周袋深度和附着丧失、患者满意率、显效时间及IL-8、IL-1β和TNF-α水平进行统计及比较。结果：经研究比较发现,观察组2、4周龈沟出血指数及牙周袋深度和附着丧失均优于对照组,观察组显效时间短于对照组,患者满意率高于对照组,IL-8、IL-1β和TNF-α水平均低于对照组,P均〈0.05,均差异有统计学意义。结论：在急性牙周脓肿的治疗中,采用布洛芬缓释凝胶综合效果较佳,值得临床推广应用。     

注射用盐酸多西环素治疗急性细菌性感染的临床研究

目的评价国产注射用盐酸多西环素治疗轻、中度急性细菌性感染的临床疗效与安全性。方法采用双盲、随机对照实验设计，以注射用阿奇霉索为对照药。试验组0．2g，对照组0．5g溶解于生理盐水500ml中，（1d，静脉滴注，疗程5～12d。结果本研究共纳入84例，注射用多西环索和注射用阿奇霉素组各42例。其中盐酸多西环素组及阿奇霉索组纳入ITT分析均为42例，PP分析均为41例。疗程结束时注射用盐酸多西环素组和注射用阿奇霉素组的总痊愈率和有效率分别为73．81％与97．62％和71．43％与97．62％；两组细菌清除率分别为85．29％，75．76％；以上结果两组间比较无显著性差异（P〉0．05）。注射用盐酸多西环素组和注射用阿奇霉索组的不良反应发生率分别为7．14％和11．9％，主要表现为轻度的局部刺激症状，经减慢输液速度、湿热敷等处理后缓解。结论国产注射用盐酸多西环素治疗轻、中度急性细菌性感染的临床疗效确切，安全性较好。     

激素在鼻窦炎患者鼻内窥镜围手术期的应用

目的:探讨激素在鼻窦炎鼻内窥镜围手术期中的临床应用价值.方法:97例鼻窦炎鼻内窥镜手术患者分为治疗组51例和对照组46例,治疗组加用激素,其余治疗和对照组等同.术后随访6个月,观察两组患者的疗效.结果:治疗组治愈率82.3％,总有效率92.2％;对照组治愈率60.9％,总有效率80.4％.结论:激素作为鼻窦炎鼻内窥镜围手术期的治疗药物之一,可以使术腔清洁,加快黏膜上皮化和鼻腔鼻窦生理功能恢复,提高治愈率.     

Pharmacokinetics of oxycodone hydrochloride and three of its metabolites after intravenous administration in Chinese patients with pain

ObjectivesThe aim of this study is to evaluate the pharmacokinetic profile of oxycodone and three of its metabolites, noroxycodone, oxymorphone and noroxymorphone after intravenous administration in Chinese patients with pain.MethodsForty-two subjects were assigned to receive intravenous administration of oxycodone hydrochloride of 2.5, 5 or 10 mg. Plasma and urine samples were collected for up to 24 h after intravenous administration of oxycodone hydrochloride.ResultsPharmacokinetic parameters showed that mean values of C_max, AUC_0–t and AUC_0–∞ of oxycodone were dose dependent, whereas T_max and t_1/2 were not. The mean AUC_0–t ratio of noroxycodone to oxycodone ranged from 0.35 to 0.42 over three doses, and those of noroxymorphone, or oxymorphone, to oxycodone were ranging of 0.06–0.08 and 0.007–0.008, respectively. Oxycodone and its three metabolites were excreted from urine. Approximately 10% of unchanged oxycodone was recovered in 24 h. Most adverse events (AEs) reported were mild to moderate. The frequently occurred AEs were dizziness, nausea, vomiting, drowsiness and fatigue. No dose-related AEs were found.ConclusionOur pharmacokinetics of oxycodone injection in Chinese patients with pain strongly support continued development of oxycodone as an effective analgesic drug in China.