The comparative bioavailability of an extended-release niacin and lovastatin fixed dose combination tablet versus extended-release niacin tablet, lovastatin tablet and a combination of extended-release niacin tablet and lovastatin tablet

Lovastatin and extended-release (ER) niacin in a fixed dose combination (Advicor) is approved for the treatment of dyslipidemia. Since both drugs are extensively metabolized, this study investigated the bioavailability and pharmacokinetics of their co-administration following single-dose administration. In a 4-way crossover study 40 subjects received: two 1000/20 Advicor tablets (ADV), two 1000 mg niacin ER tablets (NSP), two 20mg lovastatin tablets (Mevacor; MEV), and two niacin ER 1000 mg tablets with two lovastatin 20mg tablets (NSP+MEV). Plasma was assayed for niacin, nicotinuric acid (NUA), lovastatin, lovastatin acid and HMGCoA reductase inhibition. Urine was assayed for niacin and its metabolites, NUA, N-methylnicotinamide and N-methyl-2pyridone-5-carboxamide. Least square mean ratios and 90% confidence intervals for C(max) and AUC((0-t)) were determined for NSP+MEV versus MEV or NSP, ADV versus MEV or NSP, and ADV versus NSP+MEV. Co-administration of niacin and lovastatin did not significantly influence C(max) and AUC((0-t)) of lovastatin, niacin, NUA and total urinary recovery of niacin and metabolites. A 22 to 25% decrease in lovastatin acid C(max) was observed while lovastatin acid AUC((0-t)) was not affected. The HMGCoA reductase inhibition C(max) and AUC((0-t)) were not affected indicating that the difference in lovastatin acid C(max) was not clinically relevant.     

Relative bioavailability of paracetamol from tablets and suppositories as well as of paracetamol and codeine in a combination tablet

Eight healthy male volunteers took part in this study to determine the relative bioavailability of Treuphadol oblong tablets (500 mg paracetamol), Treuphadol Plus oblong tablets (500 mg paracetamol, 30 mg codeine phosphate) and Treuphadol suppositories (750 mg paracetamol) against commercial tablets (500 mg paracetamol). Plasma levels of paracetamol and codeine, plus saliva levels of paracetamol for the two paracetamol only formulations, were determined by HPLC and the pharmacokinetic parameters established. The AUC data for paracetamol showed that all four preparations were bioequivalent. The saliva levels of paracetamol demonstrated a good correlation to the corresponding plasma levels. The pharmacokinetic data of codeine from the Treuphadol Plus tablet were compared with corresponding data from the literature. The bioequivalence of codeine when based on this comparison can also be assured.     

Development and validation of a dissolution test for a once-a-day combination tablet of immediate-release cetirizine dihydrochloride and extended-release pseudoephedrine hydrochloride

A dissolution test for a once daily combination tablet containing 10 mg of cetirizine dihydrochloride (cetirizine HCl) for immediate release and 240 mg of pseudoephedrine hydrochloride (pseudoephedrine HCl) for extended release was developed and validated according to current ICH and FDA guidelines. The cetirizine HCl is contained within an outer layer of the tablet while a semipermeable membrane of cellulose acetate and polyethylene glycol controls the rate at which pseudoephedrine HCl is released from the tablet core. The dissolution method, which uses USP apparatus 2 with paddles rotating at 50 rpm, 1000 ml of deaerated water as the dissolution medium, and reversed-phased HPLC for quantitation, was demonstrated to be robust, discriminating, and transferable. These test conditions were selected after it was demonstrated that the cetirizine HCl portion of the tablet rapidly dissolved in aqueous media over the physiologically relevant pH range of 1.1-7.5, and that the extended-release profile of pseudoephedrine HCl was independent of dissolution conditions (i.e., apparatus, pH, and agitation).     

Effect of food on bioavailability of pseudoephedrine and brompheniramine administered from a gastrointestinal therapeutic system

The purpose of this study was to determine how a high-fat meal affects the delivery and absorption of pseudoephedrine and brompheniramine maleate when delivered from a gastrointestinal therapeutic system (GITS). This study was a randomized, complete crossover trial with 12 healthy male volunteers who were given single doses of the 24-h GITS under fed and fasted conditions. Pharmacokinetic parameters for both drugs were comparable between fed and fasted treatments, except for a shorter time to maximum concentration of pseudoephedrine for fed subjects (p = 0.002). Bioavailability of pseudoephedrine was 91% for fed relative to fasted treatment; for brompheniramine it was 89%. These results indicate that codelivery of the two drugs from the GITS is reliable and prolonged, and that the resulting absorption of pseudoephedrine and brompheniramine is minimally affected by food.     

国产与进口地高辛片人体生物利用度的研究

目的：国产地高辛片长期以来存在着生物利用度差的问题,为此杭州民生药厂进行了工艺改进。方法：以英国Ｌａｎｏｘｉｎ片为对照,采用荧光偏振免疫分析法测定了８名健康男性受试者口服单剂量０．５ｍｇ地高辛片的药时数值,经ＰＫＢＰＮ１程序拟合,计算其药动学参数。结果：国产和进口的Ｃｍａｘ分别为３．０±０．６ｎｇ·ｍｌ－１和２．５±０．５ｎｇ·ｍｌ－１;Ｔｍａｘ分别为１．１±０．６ｈ和１．１±０．４ｈ;ＡＵＣ分别为３７．９±４．２ｎｇ·ｈ·ｍｌ－１和３７．２±６．１ｎｇ·ｈ·ｍｌ－１;杭州民生药厂工艺改进后的片剂相对生物利用度为１０３．８％±１７．０％。结论：国产片与进口片地高辛完全等效。这为临床应用提供参考,也为药品的国际接轨提供依据     

二氟尼柳片剂人体相对生物利用度

目的比较二氟尼柳片剂与胶囊剂人体药物动力学和生物利用度.方法采用高效液相色谱法测定10名健康志愿者单次口服500mg片剂或胶囊剂后,二氟尼柳在血浆中的药物浓度,计算两者的药物动力学参数和相对生物利用度.结果二氟尼柳片剂和胶囊剂人体药-时曲线符合一室开放模型,其主要药物动力学参数T1/2分别为(10.46±1.33)和(10.75±2.21)h;cmax分别为(30.76±3.20)和(29.93±2.26)mg/L;tmax分别为(2.22±0.31)和(2.13±0.61)h;MRT分别为(17.33±1.84)和(17.48±2.88)h;AUC0→t分别为(434.33±53.21)和(428.55±68.00)mg*h/L;二氟尼柳片剂对胶囊剂的相对生物利用度为(102.2±8.94)%.两制剂的AUC、cmax及lnAUC、lncmax经方差分析和双单侧检验法证明无显著性差异(P＞005).结论二氟尼柳片剂和胶囊剂具有生物等效性.     

盐酸伪麻黄碱缓释片在健康志愿者中的药动学

目的研究盐酸伪麻黄碱缓释片(S-PSE)的药动学特征。方法12例健康志愿者,单次口服S-PSE240mg,用高效液相色谱法测定血药浓度。结果S-PSE的药动学参数分别为MRT(18.3±1.7)h,Tpeak(7.7±1.9)h,Cmax401.5±60.6)ng*ml-1。结论研制的S-PSE的主要药动学参数与国外文献报道的基本一致。     

盐酸伪麻黄碱缓释片的相对生物利用度和稳态药物动力学

目的研究盐酸伪麻黄碱(Pse)缓释片的相对生物利用度及稳态药物动力学.方法12名健康志愿者单剂量或多剂量口服Pse缓释片或普通片,用高效液相色谱法测定血药浓度.结果Pse缓释片的相对生物利用度为(100.3±7.496)%.多剂量口服Pse缓释片和普通片稳态药物动力学参数AUC(0→t)(5626±980.8)和(1393±211.0)ng*h/ml,cmin(110.0±26.37)和(115.3±24.61)ng/ml,cmax(394.1±56.79)和(427.9±96.09)ng/ml以及FI∶1.126±0.179和1.19±0.137.结论研制的Pse缓释片可缓释24h,并与口服60mg,q6h普通片生物等效.其主要药物动力学参数与国外文献报道的基本一致.     

布洛伪麻软胶囊的药物动力学及相对生物利用度考察

目的研究布洛伪麻软胶囊在健康人体内的药物动力学及相对生物利用度。方法采用HPLC法测定20名健康男性受试者口服布洛伪麻软胶囊和洛芬伪麻片后不同时间血浆中布洛芬和盐酸伪麻黄碱的质量浓度,并求出主要药物动力学参数。结果血浆中布洛芬的tmax分别为(1.4±0.9)和(2.6±1.2)h,ρmax分别为(43.7±10.2)和(35.6±8.8)mg.L-1,t1/2均为(2.4±0.5)h,AUC0-15分别为(177.9±39.7)和(165.1±42.2)mg.h.L-1;盐酸伪麻黄碱的tmax分别为(1.3±0.2)和(1.2±0.2)h,ρmax分别为(296.6±98.8)和(269.5±82.5)μg.L-1,t1/2分别为(5.4±0.4)和(5.4±0.3)h,AUC0-24分别为(1.943±0.394 1)和(1.952±0.399 5)mg.h.L-1;布洛芬的相对生物利用度为(107.8±8.3)%,盐酸伪麻黄碱的相对生物利用度为(99.5±5.4)%。结论根据双单侧检验表明两种制剂具有生物等效性。     

Effect of food on the bioavailability of oxybutynin from a controlled release tablet

Objective: The effect of food on the bioavailability of oxybutynin was assessed in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg dose of a controlled release oxybutynin tablet was administered after a high fat breakfast and to fasting subjects. The AUC, C_max, t_max, t_1/2 and MRT of oxybutynin and its active metabolite N-desethyloxybutynin were determined. Results: Breakfast did not change the AUC of oxybutynin but increased the AUC of N-desethyloxybutynin by about 20% . The C_max of oxybutynin and N-desethyl oxybutynin were two-fold higher when the drug was administered after breakfast compared to the fasting state. Conclusion: Breakfast significantly reduced the MRT of oxybutynin and N-desethyloxybutynin. Received: 6 October 1995/Accepted in revised form: 26 February 1996     

青霉素V钾胶囊与片剂的药物动力学及相对生物利用度比较

目的比较青霉素V钾胶囊与片剂的药物动力学及相对生物利用度.方法以微生物法测定10名健康受试者单次空腹po青霉素V钾胶囊和片剂500mg后血、尿药浓度.结果po青霉素V钾胶囊和片剂后的体内过程符合二室模型.其平均cniax分别为(8.22±1.21)和(7.71±1.09)mg/L,tniax为(0.55±0.11)和(0.58±0.17)h,T1/2ka为(0.21±0.09)和(0.20±0.06)h,T1/2β为(0.81±0.21)和(0.72±0.08)h,AUC为(9.51±1.06)和(9.50±1.82)h@mg/L,24h累积尿排出率分别为给药量的(35.33±7.45)%和(37.80±5.45)%.青霉素V钾胶囊与片剂的药物动力学参数间差异无统计学意义(P＞0.05).结论青霉素V钾胶囊的相对生物利用度为(101.44士9.59)%,与片剂具生物等效性.     

盐酸氟桂利嗪片的人体相对生物利用度

目的:比较盐酸氟桂利嗪(A)与参比片(B)的药物动力学和相对生物利用度.方法:采用HPLC荧光法测定10名健康受试者po 24mg A和B后,盐酸氟桂利嗪在血浆中的浓度,计算两者的药物动力学参数和相对生物利用度.结果:A和B的AUC_(0—∞)分别为(481.82±21.33)、(497.24±36.03)(μg·h)/L,t_(?)分别为(3.69±0.27)、(3.69±0.32)h,C_(?)分别为(4O.29±2.71)、(40.89±3.6Oμg/L,两者的AUC,t_(?)、c_(?)均无显著性差异(P>0.05).采用梯形法计算两者的AUCO_(0—t)分别为(459.26±14.75)、(468.32±34.44)(μg·h)/L,A的相对生物利用度为(98.4±6.6)%.结论:被试片剂与参比片剂具有生物等效性.     

Comparative bioavailability of a microcrystalline theophylline tablet and uncoated aminophylline tablets

Summary The bioavailability of a rapidly dissolving tablet of theophylline and three brands of standard aminophylline tablets was estimated in a four way cross-over study involving 8 healthy adult volunteers. The relative extent of bioavailability as assessed by the measurement of the total area under the plasma concentration time curves showed no difference between the products (P>0.05). Computed estimates of the rate of drug absorption were similar for all 4 products tested. The results indicate that the rapidly dissolving tablet offers no advantage in respect to rate and extent of absorption over conventional aminophylline tablets.     

In vitro and in vivo assessment of the bioavailability of potassium from a potassium tartrate tablet

The bioavailability of potassium from orally administered potassium tartrate was evaluated in 20 normal subjects under metabolic balance conditions. Subjects were given 34 mmol potassium (5 tablets of Cal-K) as a divided dose on each of 2 consecutive days. Urinary excretion of potassium, as determined from 24-h urinary collections on the 3 days preceding dosage totalled 192.6 +/- 50.9 mmol (mean +/- S.D., n = 20). It increased significantly (p less than 0.05) to 258.7 +/- 54.2 mmol for the 2 days of dosage and the following day. The difference of 66.1 mmol representing absorbed potassium was close to the 68 mmol potassium given and indicated a bioavailability of potassium in excess of 97 per cent; after correction for creatinine excretion, potassium recovery rose to 99.9 per cent. The dissolution characteristics of the Cal-K tablets were also determined. After dissolution in simulated gastric juice (pH 1.2), 84.4 +/- 10.6 per cent (mean +/- S.D., 6 experiments) was dissolved; after adjustment to pH 7.3, dissolved potassium increased to 91.3 +/- 8.5 per cent. No precipitation or residue formed as a result of the pH change. Both sets of results indicate that potassium from these potassium tartrate tablets is in a highly bioavailable form.     

Plasma concentrations and bioavailability of isosorbide dinitrate and pindolol from a combination formulation

The plasma concentrations and bioavailability of sustained-release isosorbide denigrate and standard-release pindolol have been compared after administration of these drugs in combination and alone. Bioavailability parameters of isosorbide dinitrate and pindolol obtained after administration of the drugs in combination were not significantly different (P>0.05) to those obtained after administration of either drug alone. Two peaks of mean concentrations of isosorbide dinitrate occurred in plasma after administration of 30 mg of this drug in combination with 7.5 mg pindolol (4.4 ng ml^?1 at 1 h and 4.5ng ml^?1 at 5h), or alone (5.9ngml^?1 at 2h and 5.7ng ml^?1 at 5h). In each case, plasma concentrations of isosorbide dinitrate were maintained during at least 8 h, whereas the drug was not detected in plasma at 2.5 h after administration of a standardrelease formulation. The peaks of mean concentrations of pindolol were 39.7ng ml^?1 at l.5h after administration of 7.5 mg drug in combination with isosorbide dinitrate and 38.0 ng ml^?1 at 1 h after administration of the drug alone. Concentrations of pindolol in plasma declined with a half-life of 3 h.     

尼莫地平漂浮缓释片的人体药物动力学及相对生物利用度

目的:比较尼莫地平(Nim)漂浮缓释片与普通片的药物动力学、相对生物利用度及体内外相关性.方法:10例男性健康受试者自身交叉对照、单剂量po Nim漂浮缓释片或普通片各120mg,采用HPLC法测定血浆Nim浓度,单室模型拟合药物动力学参数.结果:Nim缓释片和普通片的t_(max)分别为(2.83±0.45)和(0.87±0.27)h(P<0.01),C_(max)分别为(32.82±6.36)和(48.71±8.94)ng/ml(P<0.01),AUC分别为(204.81±45.03)和(159.98±39.96)h·ng/ml(P<0.01).数据经对数转换后进行双单侧检验,两种制剂生物不等效;缓释片的相对生物利用度为(129.89±17.02)%;其体内吸收与体外释药具有显著的相关性(P<0.01).结论:Nim漂浮缓释片生物利用度优于普通片,达到剂型设计要求.     

双波长薄层扫描法测定异麻匹林片中咖啡因和盐酸伪麻黄碱含量

目的 测定异麻匹林片中咖啡因和盐酸伪麻黄碱的含量。方法 双波长薄层扫描,咖啡因的测定波长λｓ＝２７０ｎｍ,λＲ＝３５０ｎｍ,盐酸伪麻黄碱的λｓ＝５１０ｎｍ,λＲ＝６１０ｎｍ,展开剂为氯仿－醋酸乙酯－甲醇－氨水（１５：４：３：０．３）。结果咖啡因和盐酸伪麻黄碱的平均回经分别为９９．０％和９９．８％,ＲＳＤ分别为１．９％和０．８％。结论 该法简单、快速、结果准确,适合于该制剂的质量控制。