不同厂家特非那丁片溶出度考察

:采用高效液相色谱法测定不同厂家生产的特非那丁片溶出度 ,以考察其质量。结果表明 :3个厂家 4个批号样品溶出度存在显著性差异。     

用高效液相法对特非那定片溶出度的研究

目的:考察药厂间特非那定片的溶出度,评价其内在质量。方法:采用HPLC法测定特非那定片剂溶出度,色谱柱:KF-C18;流动相:乙腈-水-磷酸盐缓冲液-二乙胺(250:200:60:4),用磷酸调pH至6.0;检测波长:235nm。结果:三家国产特非那定片在1000ml0.1mol·L-1盐酸溶液中溶出度差异较大。仅B药厂溶出度较好(40min,溶出度>75%)。     

不同药厂特非那定片溶出度考察

目的：考察不同药厂特非那定片的溶出度,评价其内在质量。方法：采用ＨＰＬＣ法测定了特非那定片剂溶出度,色谱柱：ＫＦＣ１８;流动相：乙腈水磷酸盐缓冲液二乙胺（５００∶４００∶１００∶６）,用磷酸调节ｐＨ至６．０;检测波长：２３５ｎｍ。结果：三家国产特非那定片在９００ｍｌ０．１ｍｏｌ·Ｌ－１盐酸溶出介质中溶出度差异较大,４５ｍｉｎ平均溶出度（ｎ＝６）分别为：２１．９３％（Ａ厂）,８５．２９％（Ｂ厂）,３７．２２％（Ｃ厂）,仅Ｂ厂片剂符合ＵＳＰⅩⅩⅢ版中特非那定片剂溶出度标准（４５ｍｉｎ溶出度＞７５％;片剂溶出度均一性较差,４５ｍｉｎ取样点ＲＳＤ分别为：６８．８６％（Ａ厂）,９．３６％（Ｂ厂）,１６．５８％（Ｃ厂）。结论：为了确保特非那定临床疗效,国产片剂质量标准中应增加溶出度检查项目     

特非那丁片溶出度的探讨

建立了以紫外分光光度法测定特非那丁含量的方法,具有线性范围好、稳定、快速、灵敏的特性,适用于对特非那丁片溶出度及相关实验的研究。本实验以０．１ｍｏｌ／Ｌ的盐酸为介质,对四个厂家共１５批次的特非那丁片剂进行体外溶出的研究。结果表明：四个厂家不同批号的特非那丁片之间的实验结果具有显著性差异。     

特非那定片的溶出度研究

目的：改进特非那定片的处方工艺,改善溶出度。方法：参照国外处方并根据国内辅料情况筛选新的片剂工艺方法。将不同处方生产的片剂按《中国药典》规定的方法进行溶出度检查。结果：按新处方、老处方生产的片剂与德国史达特公司生产的片剂在４５分种时的溶出分别为８９．０２％、１０．８１％和８２．３６％。结论：特非那定片处方组成对溶出度尤为重要,新处方中碳酸氢钠的加入使其溶出度明显提高。     

高效液相色谱法测定特非那丁片溶出度

目的：通过对国内３个厂家生产的特非那丁片溶出度测定,考察其质量。方法：转篮法,用高效液相色谱法检测,提取参数（Ｔ５０、Ｔｄ、ｍ）,并对参数进行相关性检验。结果：不同厂家产品溶出参数差异显著。结论：对国内厂家的特非那丁片有必要增加溶出度考察,以控制其质量。     

特非那定片的体外溶出度考察

特非那定为H受体拮抗剂，具有特异的外周H受体拮抗作用，有抗5-羟色胺、抗胆碱和抗肾上腺素能的作用。为目前临床上常用的抗过敏药物，主要用于过敏性鼻炎、荨麻疹及枯草热的治疗[1]。国内生产厂家较多，临床疗效也反映不一。为此，我们对国产5个厂家的6批特非那定片进行了溶出度测定，以考察其内在质量。1仪器与试药1．1仪器；ZRS－6智能药物溶出仪（天津大学精密仪器厂）；Waters515型高效色谱仪；uBOndparkC183．9*300mm10um不锈钢柱。1．2试药：持非那定片（规格均为每片60mg）；特非那定对照品（符合《中国药典》1995的年版标准）…     

不同厂家曲克芦丁片的体外溶出度考察

目的：对国内4个厂家的6个批号曲克芦丁片进行质量评价。方法：采用转篮法和紫外分光光度法进行含量和溶出度测定。结果：4个厂家的6个批号曲克芦丁片60 min溶出度分别为88.56%，41.32%，89.69%，73.18%，70.14%，92.06%。结论：不同厂家曲克芦丁片的溶出度有明显差异。建议对曲克芦丁片进行溶出度监测，确保药品质量。     

尼卡地平片溶出度测定

采用紫外分光光度法对三个厂家四个批号的尼卡地平片进行溶出度测定，求得的Ｔ５０、Ｔｄ和ｍ参数具有显著性差异（Ｐ＜０．０１），提示尼卡地平片有必要把溶出度测定作为其质量控制标准之一。     

过程分析考察不同厂家盐酸维拉帕米片的溶出度

目的：利用光纤溶出度过程分析方法,监测盐酸维拉帕米片的溶出度,反映不同厂家及同一厂家不同批号盐酸维拉帕米片间的质量差异.方法：采用《中国药典》盐酸维拉帕米片溶出度检测方法中的条件,利用光纤传感溶出度实时过程分析方法考察4个不同厂家及同一厂家5个不同批号盐酸维拉帕米片的溶出度.结果：过程溶出曲线反映每一药片溶出过程全部信息.4个不同厂家盐酸维拉帕米片的溶出度均符合《中国药典》2010年版规定,但溶出速度和曲线存在差异.结论：光纤溶出度过程分析原位实时反映了药物体外溶出特性,并真实地反映了同一药物的药片存在明显的差异.对考察体内外相关性、评价药品品质和评价生物等效性提供了有效途径.     

Population variability in the pharmacokinetics of terfenadine: the case for a pseudo-polymorphism with clinical implications

Terfenadine is nearly completely first pass biotransformed. Unmetabolized terfenadine plasma concentrations have been associated with altered cardiac repolarization. During previous drug interaction studies, 2 subjects were found to have quantifiable concentrations of unmetabolized terfenadine with accompanying electrocardiographic repolarization changes while on terfenadine alone. To determine whether these subjects were representative of the population, 150 healthy volunteers (109 males, 41 females, ages 19-49) were screened for their ability to metabolize terfenadine after achieving steady-state. Blood was obtained at known times of maximum terfenadine concentration after dosing. Eleven subjects had quantifiable concentrations of terfenadine demonstrating wide intersubject variability in terfenadine metabolism. Further studies to determine whether such subjects are more susceptible to untoward terfenadine-associated events are underway.     

Itraconazole prevents terfenadine metabolism and increases risk of torsades de pointes ventricular tachycardia

Summary Terfenadine, a nonsedating H₁-selective antihistamine, is widely used in many countries. We report pharmacokinetic results in a patient who developed a prolonged QT-interval in ECG and symptomatic torsades de pointes ventricular tachycardia as a consequence of the interaction of itraconazole and terfenadine. Both drugs were taken in the recommended doses: terfenadine 60 mg b.d. and itraconazole 100 mg b.d.Terfenadine metabolism was delayed by itraconazole, leading to an increased level of unmetabolised terfenadine. Seven weeks after the cessation of itraconazole treatment, terfenadine was rapidly metabolized to its active metabolite and did not prolong the QT-interval when given as a single provocation dose (120 mg).The findings suggest that intraconazole in therapeutic doses inhibits terfenadine metabolism. It is also possible that unmetabolised terfenadine alone, without an increased level of its active metabolite, may cause torsades de pointes. The concomitant use of terfenadine and itraconazole (and ketoconazole) should be avoided.     

Actions of terfenadine and cimetidine on histamine wheal formation.

1. A Latin square design was used to compare the effects of four masked oral drugs, placebo, cimetidine, terfenadine and cimetidine plus terfenadine, at single standard doses against histamine injected at concentrations of 0.3 mM and 0.074 mM subepidermally in eight healthy volunteers studied at weekly intervals. 2. Wheal growth occurred in three phases, an initial delay, a phase of rapid growth where drugs were effective, and a phase of slow growth where there were no significant drug effects. 3. Terfenadine was an effective antihistamine. 4. The data were consistent with a terfenadine effect continued into the next treatment block. 5. Under these conditions cimetidine apparently reduced the effects of terfenadine during the rapid wheal growth phase both simultaneously and after a week's interval from terfenadine dosing.     

Evaluation of terfenadine and ketoconazole-induced QT prolongation in conscious telemetered guinea pigs

Terfenadine and ketoconazole are the most widely used positive reference agents in non-clinical cardiac repolarization safety studies. The aim of the present study was to evaluate the effects of terfenadine, ketoconazole and their combination on QT prolongation using conscious guinea pigs. Conscious telemetered guinea pigs were orally administered terfenadine (50 mg/kg), ketoconazole (200 mg/kg) or a combination of the two, and effects on QT were recorded using a telemetry system. The QT correction was carried out with Bazett's formula to eliminate confounding effect of HR. Neither terfenadine nor ketoconazole produced any effect on the RR and QT intervals, QRS complex or heart rate (HR). However, a combination of terfenadine and ketoconazole significantly prolonged the RR and QT intervals and decreased HR in a time-dependent manner. This study demonstrated that the combination of terfenadine and ketoconazole produces QT prolongation in conscious telemetered guinea pigs.     

Effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide in volunteers.

The effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide (VIP) was studied in 7 healthy subjects and 8 subjects with the common cold. Before terfenadine administration, the mean plasma substance P concentration of the subjects with the common cold was significantly higher than that of the healthy subjects. The increased mean plasma substance P concentration of the subjects with the common cold was decreased after terfenadine administration. In the healthy subjects, the mean plasma substance P concentration was unchanged by terfenadine administration. The mean plasma VIP concentration of the subjects with common cold was slightly higher than that of the healthy subjects before and after terfenadine administration, with no significant difference.     

Terfenadine-antidepressant interactions: an in vitro inhibition study using human liver microsomes

AIMS: Inhibition of the metabolism of terfenadine has been associated with torsades de pointes ventricular arrhythmias. The aim of this study was to assess in vitro the potency of the antidepressants nefazodone, sertraline and fluoxetine in inhibiting terfenadine biotransformation. METHODS: Human liver microsomes were incubated with terfenadine and the antidepressants at various concentrations. Formation of the two major metabolites of terfenadine was determined by h.p.l.c. RESULTS: The apparent Km for microsomes from four human livers was 11+/-5 and 18+/-3 microM (mean +/-s.e.mean) for the N-dealkylation and C-hydroxylation pathways, respectively. Nefazodone, sertraline and fluoxetine inhibited terfenadine N-dealkylation with K(i) values of 10+/-4, 10+/-3 and 68+/-15 microM respectively. Inhibition of the C-hydroxylation pathway yielded noncompetitive K(i) values of 41+/-4, 67+/-13 and 310+/-40 microM respectively. CONCLUSIONS: Nefazodone and sertraline were moderately weak in vitro inhibitors of terfenadine metabolism while fluoxetine was a very weak inhibitor. Clinically significant interaction of terfenadine is more likely with nefazodone than sertraline or fluoxetine since therapeutic plasma levels of nefazodone are comparatively higher.     

Effect of concomitant administration of cimetidine and ranitidine on the pharmacokinetics and electrocardiographic effects of terfenadine

Summary Terfenadine is a widely prescribed non-sedating antihistamine which undergoes rapid and almost complete first pass biotransformation to an active carboxylic acid metabolite. It is unusual to find unmetabolised terfenadine in the plasma of patients taking the drug. Terfenadine in vitro is a potent blocker of the myocardial potassium channel. Overdose, hepatic compromise and the coadministration of ketoconazole and erythromycin result in the accumulation of terfenadine, which is thought to be responsible of QT prolongation and Torsades de Pointes ventricular arrhythmia in susceptible individuals. Cimetidine and ranitidine are two popular H₂ antagonists which are often taken with terfenadine. The effects of cimetidine and ranitidine on terfenadine metabolism were studied in two cohorts of 6 normal volunteers given the recommended dose of terfenadine (60 mg every 12 h) for 1 week prior to initiation of cimetidine 600 mg every 12 h or ranitidine 150 mg every 12 h. Pharmacokinetic profiles and morning pre-dose electrocardiograms were obtained whilst the patients were on terfenadine alone and after the addition of cimetidine or rantidine.One of the subjects in each cohort had a detectable plasma level of parent compound after 1 week of terfenadine therapy alone; it did not accumulate further after addition of the H₂ antagonist. The pharmacokinetics of the carboxylic acid metabolite of terfenadine (C_max, t_max, AUC) were not significantly changed after co-administration of either H₂ antagonist. None of the remaining 5 subjects in either cohort demonstrated accumulation of unmetabolised terfenadine after addition of the respective H₂ antagonist and electrocardiographic QT intervals and T-U morphology in them was not changed during the course of the study.We conclude that cimetidine and ranitidine in the dosages used in this study did not affect the metabolism of terfenadine, and that patients exposed to these drug combinations are not at increased risk of altered cardiac repolarisation.The views expressed in this article are those of the authors and do not reflect the official policy of the Uniformed Services University, Walter Reed Army Medical Center, Department of Defense or the Food and Drug Administration     

Lack of effect of terfenadine on the pharmacokinetics of the CYP3A4 substrate buspirone

The effects of terfenadine, a non-sedating antihistamine on the pharmacokinetics and pharmacodynamics of buspirone, a CYP3A4 substrate, were investigated in a randomised, placebo-controlled, two-phase cross-over study. Ten healthy volunteers took either 120 mg terfenadine or matched placebo orally once daily for 3 days. On day 3, 10 mg buspirone was taken orally. Plasma concentrations of buspirone were measured up to 18 hr and its pharmacodynamic effects up to 8 hr. Terfenadine slightly but not significantly increased plasma concentrations of buspirone. No psychomotor deterioration was observed during the terfenadine phase. In conclusion, terfenadine did not significantly affect the pharmacokinetics of buspirone, a CYP3A4 substrate shown to be very susceptible to interactions with CYP3A4 inhibitors. Thus, terfenadine is expected to have little effect on the pharmacokinetics of CYP3A4 substrates in general.     

Comparison of the central and peripheral effects of cetirizine and terfenadine

Summary The peripheral and central effects of 10 mg cetirizine 2 HCl and 60 mg terfenadine have been compared with placebo in 9 healthy male volunteers.The peripheral effect, in terms of cutaneous reactivity to 1 µg histamine i.d., was measured by planimetry of the wheal and erythemas. Central effects were assessed with a self-evaluation visual scale and from the results of electroencephalographic spectrum analysis. Peripheral inhibition of histamine reactivity was more intense and quicker for cetirizine than for terfenadine. On the self-evaluation scale, no significant difference between terfenadine, cetirizine and placebo was noted. The quantified EEG did not show any variation in spectral parameters at any time after cetirizine. By contrast, at 6 h terfenadine had increased slow waves and had inhibited the alpha band. Thus, 10 mg cetirizine 2 HCl had less effect on the central nervous system than terfenadine 60 mg, whilst its peripheral action appeared more quickly and was more intense.