Receptor binding assays in analysing the bioavailability and pharmacodynamic bioequivalence of active drug moieties

The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its ₁-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung ₁-and rat reticulocyte ₂-adrenoceptors.The formulations differed markedly in their kinetic characteristics: the peak plasma concentration (C_max) of R,S-metoprolol after administration of the conventional formulation was 140 ng·ml^–1, (n=7) and it was approximately one-third of that after the sustained-release formulation, 49 ng·ml^–1, (n=6); the AUC_{0–24 h}-values for the formulations were 700 and 310 ng·h·ml^–1, respectively. The C_max for the ₁-adrenoceptor binding component of metoprolol was 180 ng·ml^–1 (n=7) after administration of the conventional, and 74 ng·ml^–1 after administration of the sustained-release formulation. The corresponding AUC_{0–24 h}-values for the receptor binding component were 920 and 470 ng·h·ml^–1 (n=7).Thus, the kinetic differences between R,S-metoprolol and the ₁-receptor binding component were considerable and they were affected by the type of formulation. In general, after administration of the sustained-release formulation, the percentage ₁- and ₂-adrenoceptor occupancy of metoprolol in plasma was 5–15% less than after administration of the conventional formulation. At 0.5–1.5 h after drug intake the average ₁-adrenoceptor occupancy of the conventional formulation varied between 80–90% and that of the sustained release formulation between 20–76%. At these times the differences in receptor occupancy were significant; at 0.5–2 h after drug intake the average ₂-adrenoceptor occupancy of the conventional formulation varied from 20–30%, and that of the sustained-release formulation was 2–17%. At other times the difference in receptor occupancy between the formulations was not significant.The results demonstrate that plasma concentration-kinetics were more discriminating than -adrenoceptor-binding in analysing bioequivalence. It was possible to determine the bioavailability of the active ingredient of metoprolol and to study pharmacodynamic bioequivalence by using receptor binding assays.     

HPLC-MS法快速测定人血浆中洛索洛芬钠的浓度及其药代动力学研究

目的:建立一种快速测定人血浆中洛索洛芬钠含量的方法,并应用于测定洛索洛芬钠的血药浓度,计算其药代动力学参数和相对生物利用度。方法:0.2 ml酸化的血浆样品经正己烷-乙醚(4 1,v/v)提取,色谱柱为Diamonsil 150 mm×2.1 mm,5μm,C18柱,流动相为0.2%醋酸铵-乙腈(25 75,v/v);采用ESI离子源,选择性离子检验法检测血浆中的洛索洛芬。20名健康志愿者随机交叉服用洛索洛芬钠受试和参比制剂后,用LC-MS法测定人血浆中洛索洛芬的药物浓度。结果:洛索洛芬浓度0.10~10.0 g.ml-1线性关系良好(r=0.9997),绝对回收率高于80%;日内、日间RSD均小于15%。用该方法测得受试制剂和参比制剂的Cmax分别为7.17±1.63和6.94±1.33μg.ml-1,Tmax分别为0.46±0.23和0.46±0.28 h,AUC0-10分别为11.65±1.38和11.19±1.83μg.ml-1.h,AUC0-∞分别为12.04±1.42和11.64±1.89μg.ml-1.h。结论:该方法快速灵敏准确,适用于人体生物利用度研究。洛索洛芬钠受试制剂的相对生物利用度为(105.3±11.5)%。受试制剂与参比制剂生物等效。     

对乙酰氨基酚栓剂人体相对生物利用度和生物等效性

目的:研究进口试验制剂与国产对乙酰氨基酚栓剂(参比制剂)的相对生物利用度和生物等效性.方法:采用HPLC法测定18例健康男性志愿者单次交叉直肠给予参比制剂2粒(300mg)及试验制剂2粒(250mg)后的血药浓度,经CRFB软件处理,计算其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:试验制剂和参比制剂的t1/2分别为(3.94±1.54)和(3.81±1.24)h;Tmax分别为(1.56±0.57)和(1.58±0.43)h;平均滞留时间MRT0～tn分别为(5.67±1.44)和(5.40±1.28)h;Cmax分别为(1.73±0.38)和(1.61±0.34)μg·mL-1;AUC0～tn分别为(8.01±2.20)和(7.54±1.82)μg·h·mL-1.试验品与参比品的相对生物利用度为(109.07±27.92)%,经统计学处理,试验品AUC0～t的90%置信区间为97.20%～115.85%,Cmax的90%置信区间为98.64%～116.97%.结论:两制剂生物等效.     

替硝唑片的相对生物利用度及其生物等效性评价

目的研究替硝唑片在健康人体内的药代动力学及相对生物利用度。方法以 18名健康志愿者为试验对象 ,采用同体交叉试验方法 ,单剂量口服 1 0 g替硝唑片后 ,用高效液相色谱法测定血浆中药物浓度。结果达峰时间分别为 (1 72± 0 4 6 )h和 (1 6 7± 0 77)h ;达峰质量浓度分别为(18 4 2± 1 15 )mg·L-1和 (16 5 2± 1 81)mg·L-1;消除半衰期分别为 (11 92± 1 6 8)h和(13 0 2± 1 92 )h ;药时曲线下面积 (AUC0→ 60 )分别为 (32 1 2 4± 2 4 39)mg·h·L-1和 (32 9 33±32 12 )mg·h·L-1。结论被试制剂与对照制剂两种制剂生物等效。     

Lack of pharmacokinetic bioequivalence between generic and branded amoxicillin formulations. A post-marketing clinical study on healthy volunteers

AIMS

There are concerns about the quality of generic drugs in the postmarketing setting. The aim was to establish whether two generic formulations of amoxicillin, available on the Italian market, fulfil the criteria for clinical pharmacokinetic bioequivalence vs. the branded drug.

METHODS

Two generic amoxicillin products (generic A and B) were selected among four fast-release tablet formulations available on the Italian market. Twenty-four healthy adult volunteers of either sex participated to a single-dose, randomized, three-treatment, crossover, single-blind bioequivalence study designed to compare generic A and B with branded amoxicillin. Plasma samples were collected at preset times for 24 h after dosing, and assayed for amoxicillin levels by high-performance liquid chromatography.

RESULTS

Ninety percent confidence intervals of AUC ratios were 0.8238, 1.0502 (ratio 0.9302) and 0.8116, 1.1007 (ratio 0.9452) for generic A and B vs. branded amoxicillin, respectively. Ninety percent confidence intervals of C_max ratios were 0.7921, 1.0134 (ratio 0.8960) and 0.8246, 1.1199 (ratio 0.9610) for generic A and B vs. branded amoxicillin, respectively. The mean pharmacokinetic profiles showed that the AUC value of branded amoxicillin was 8.5 and 5.4% greater than that estimated for generic A and B, respectively. Few adverse events were recorded; these were not serious and occurred without apparent relationship to any specific amoxicillin formulation.

CONCLUSIONS

These results indicate that one of the two marketed amoxicillin generics analysed in the present study is not bioequivalent to the brand leader product for C_max on the basis of single-dose pharmacokinetic assessment.     

HPLC测定人血浆中茴三硫代谢产物对羟基茴三硫及相对生物利用度

目的:建立了人血浆中茴三硫代谢产物对羟基茴三硫的HPLC测定法,研究2种茴三硫片在正常人中的相对生物利用度。方法:以吴茱萸次碱为内标,血样采用乙酸乙酯(5%异丙醇)1次提取,经Diamonsil C_(18)柱分离后在355nm波长处测定。20名健康志愿者采用自身对照随机交叉试验设计,分别单剂量口服茴三硫75mg后测定两者相对生物利用度。结果:对羟基茴三硫与内标分离度好,内源性杂质不干扰测定,对羟基茴三硫的线性范围为15.6～2000ng·mL~(-1),最低检测限为10ng·mL~(-1),提取回收率在80%以上;日内、日间精密度的相对标准偏差均小于10%。单次服用75mg茴三硫片试验制剂或参比制剂后的药代动力学参数AUC(0→12)分别为(971.8±368.0)ng·h·mL~(-1)和(1004.6±391.7)ng·h·mL~(-1),C_(max)分别为(323.3±209.4)ng·mL~(-1)和(279.5±107.0)ng·mL~(-1),T_(max)分别为(1.5±0.3)h和(1.6±0.4)h。相对生物利用度为97.3±6.8%。结论:该方法快速,简便,灵敏,重复性好,可用于对羟基茴三硫在人体内过程研究。方差分析结果表明2种制剂的主要药代动力学参数之间无明显差异,双单侧t检验结果表明两种制剂为生物等效制剂。     

Development and evaluation of nasal formulations of ketorolac

Ketorolac tromethamine is a potent non-narcotic analgesic with moderate anti-inflammatory activity. Clinical studies indicate that ketorolac has a single dose efficacy greater than morphine for postoperative pain and has excellent applicability in the emergency treatment of pain. Due to incomplete oral absorption of ketorolac, several approaches have been tried to develop a nonoral formulation in addition to injections, especially for the treatment of migraine headache. The aim of our study was to develop a nasal formulation of ketorolac with a dose equivalent to the oral formulation. A series of spray and lyophilized powder formulations of ketorolac were administered into the nasal cavity of rabbits, and their pharmacokinetics profiles were assessed. The spray and powder formulations were compared through their pharmacokinetics parameters and absolute bioavailability. Drug plasma concentration was determined using solid phase extraction, followed by an HPLC analysis. Nasal spray formulations were significantly better absorbed than powder formulations. A nasal spray formulation of ketorolac tromethamine showed the highest absorption with an absolute bioavailability of 91%. Within 30 min of administration, the plasma concentration was comparable to that resulting from an intravenous injection. The absolute bioavailability of a solution of ketorolac acid was 70%. Apparently, the dissolution of ketorolac acid into the mucous layer limits its absorption. There were no significant differences in absorption between different powder formulations. Even the reduction of particle size from 123 θ m to 63 θ m did not indicate better absorption of ketorolac tromethamine from powder formulations. Interestingly, the absolute bioavailability of ketorolac tromethamine from a powder formulation is only 38%, indicating that the drug may not be totally released from the polymer matrix before it is removed from nasal epithelium by mucociliary clearance.     

比较国产与进口利鲁唑片的人体生物等效性

目的:研究利鲁唑片在正常人体内的药动学.方法:采用随机交叉设计,20例健康男性受试者随机交叉口服国产利鲁唑片和进口片剂,服药后0.25～24h内间隔取血.血样加入内标β-奈酚经预处理后用HPLC测定.计算主要药动学参数,并以进口片剂为参比制剂,估算国产利鲁唑片的生物利用度,判断生物等效性.结果:利鲁唑参比片和供试片的药-时曲线均符合二房室模型,其AUC0～24分别为(2 420.1±659.1)和(2 302.8±620.7)μg·h·L-1(P＞0.05);Cmax分别为(654.5±143.1)和(686.1±154.8)μg·L-1(P＞0.05);t1/2分别为(9.48±3.80)和(8.86±3.18)h(P＞0.05);Tmax分别(0.84±0.34)和(0.74±0.24)h(P＞0.05).以进口制剂为对照,用AUC0～24计算的国产片生物利用度为(96.19±12.89)%.结论:本实验建立的分析方法灵敏、准确、简便,统计学结果表明两制剂生物等效.     

Pharmacokinetic properties and clinical efficacy of once-daily sustained-release naproxen

Summary The pharmacokinetics and clinical efficacy of a once-daily sustained-release formulation of naproxen (sodium salt) have been compared with those of conventional-release agents.In a single dose pharmacokinetic study, the rate of absorption of the sustained-release preparation was less than that of a conventional-release preparation but the extent of absorption was the same. As is the case with conventional-release naproxen, food decreased the rate but not the extent of absorption of the sustained-release formulation.On multiple dose administration for 7 days, the AUC and average concentrations of the sustained release preparation (1 g daily) were the same as those for conventional release preparations of naproxen sodium (250 mg four times daily) and naproxen free acid (500 mg daily). The conventional-release sodium salt was absorbed more quickly with no differences in bioavailability. A double-blind clinical comparison in patients with osteoarthritis showed the sustained-release preparation (1 g daily) to be equivalent in efficacy to conventional naproxen capsules (500 mg twice daily) but to have a significantly lower incidence of gastrointestinal side-effects.The results suggest that sustained-release naproxen sodium has potential for use as a once-daily treatment for inflammatory disease.     

盐酸氨基葡萄糖片的相对生物利用度及其生物等效性评价

目的研究盐酸氨基葡萄糖片在健康人体内的药物动力学及相对生物利用度。方法采用液相色谱质谱质谱联用法测定了18名健康男性受试者口服盐酸氨基葡萄糖片和盐酸氨基葡萄糖胶囊后不同时间血浆中氨基葡萄糖的质量浓度,并求出主要药物动力学参数。结果血浆中氨基葡萄糖的tmax分别为(3.1±0.7)和(2.9±0.8)h,ρmax分别为(636.5±310.1)和(666.0±371.3)μg.L-1,t1/2分别为(0.9±0.2)和(1.1±0.4)h,AUC0-12分别为(1 896±809.7)和(1 967±858.2)μg.h.L-1。氨基葡萄糖的相对生物利用度为(96.8±9.7)%。结论根据双单侧检验表明两种制剂具有生物等效性。     

兰索拉唑片相对生物利用度与生物等效性研究

目的研究兰索拉唑片与兰索拉唑肠溶胶囊的人体相对生物利用度和生物等效性。方法健康志愿者24例,随机交叉单剂量口服兰索拉唑片与兰索拉唑胶囊,剂量均为30 mg,洗脱期1周。分别于服药后12 h内多点抽取静脉血,高效液相色谱法测定血浆兰索拉唑浓度。计算主要药动学参数及相对生物利用度,并评价两种制剂生物等效性。结果单剂量口服兰索拉唑片与兰索拉唑肠溶胶囊后血浆中兰索拉唑Cmax分别为(949.8±329.0)和(973.2±322.2)ng/mL;tmax分别为(2.44±0.52)和(2.06±0.70)h;t1/2分别为(1.97±1.12)和(1.84±1.11)h;AUC0→12分别为(3 054±2 019)和(2 911±1 818)ng.h/mL;AUC0→∞分别为(3 398±2 825)和(3 106±2 138)ng.h/mL。Cmax、AUC0→12和AUC0→∞的90%可信区间分别为90.7%~104.0%,94.0%~110.8%和94.9%~112.2%。以AUC0→12计算,兰索拉唑片的相对生物利用度为(105.0±24.6)%。结论兰索拉唑片与兰索拉唑肠溶胶囊具有生物等效性。     

国产托瑞米芬片剂人体药代动力学及生物等效性评价

目的 评价国产和进口托瑞米芬片剂在人体生物等效性。方法 用高效液相色谱法测定20名健康受试者po 20 mg托瑞米芬后血浆中托瑞米芬的浓度。结果 国产托瑞米芬片剂和进口片剂的t_(max)分别为3.15±0.37和3.00±0.65 h,C_(max)分别为1.73±0.32和1.74±0.25 mg·L~(-1),AUC_(0-504)分别为114.41±20.04和112.73±19.92mg·h·L~(-1),t_(1/2)分别为114.12±9.16和114.32±7.38 h,国产托瑞米芬片剂相对生物利用度为(102.4±14.0)％。结论 经统计学分析,国产托瑞米芬片剂和进口片剂具有生物等效性。     

微透析取样和微柱液相色谱电化学检测法测定大鼠脑纹状体中的5-羟色胺

目的:建立一个测定生物样本中5-羟色胺的灵敏方法.方法:将微透析取样和微柱液相色谱电化学检测(LCEC)有机结合,建立灵敏的分析方法.结果:很容易地测定了自由活动大鼠脑纹状体透析液中fg-pg的5-羟色胺变化.结论:本法对生物活体研究很有用.健康大鼠脑纹状体内5-羟色胺水平是相当稳定的.     

阿莫西林克拉维酸钾的质量分析及人体生物等效性、生物利用度研究

目的：评价阿莫西林克拉维酸钾的质量,并探讨其人体生物等效性、生物利用度。方法：24例健康志愿者随机交叉口服阿莫西林克拉维酸钾片（参比制剂）或阿莫西林克拉维酸钾分散片（受试制剂）625 mg后,采用液质联用仪测定血浆中阿莫西林、克拉维酸钾的血药浓度,并计算药动学参数及评价生物等效性。结果：国产制剂不同批次的样品含量差异较小,生产质量稳定;但单个杂质及总杂质均高于进口制剂。参比制剂中阿莫西林C_max（6.836±2.453）μg·mL^-1、t_max（1.8±0.8） h、t_1/2（1.6±0.2） h、AUC_0-∞（23.2±4.2）μg·h·mL^-1;克拉维酸钾C_max（3.644±0.406）μg·mL^-1、t_max（1.5±0.4） h、t_1/2（1.5±0.3） h、AUC_0-∞（24.1±5.6）μg·h·mL^-1。受试制剂中阿莫西林C_max（6.717±2.463）μg·mL^-1、t_max（1.5±0.5） h、t_1/2（1.4±0.3） h、AUC_0-∞（23.5±5.3）μg·h·mL^-1;克拉维酸钾C_max（3.597±0.399）μg·mL^-1、t_max（1.6±0.3） h、t_1/2（1.5±0.2） h、AUC_0-∞（24.5±4.8）μg·h·mL^-1。经计算可知受试制剂的单次给药后阿莫西林的相对生物利用度为96.6%,克拉维酸钾的相对生物利用度为97.3%,受试制剂与参比制剂生物等效。结论：阿莫西林克拉维酸钾分散片含量及有关物质符合药典标准,且与阿莫西林克拉维酸钾片人体生物等效性。     

姜黄素的药动学特征及剂型改造研究进展

姜黄素（curcumin）是从郁金、姜黄、莪术等姜科植物中提取的一种酚类化合物。大量研究表明,姜黄素具有稳定性差、口服难吸收、易代谢、生物利用度低等特点,而药剂学改造是目前广大研究者用于提高姜黄素生物利用度的重要方法之一。本文就姜黄素及经药剂学改造后的姜黄素的药动学研究作一综述。     

Microdialysis combined blood sampling technique for the determination of rosiglitazone and glucose in brain and blood of gerbils subjected to cerebral ischemia

Rosiglitazone is a potent synthetic peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist which improves glucose control in the plasma and reduces ischemic brain injury. However, the pharmacokinetics of rosiglitazone in the brain is still unclear. In this study, a method using liquid chromatography-mass spectrometry coupled with microdialysis and an auto-blood sampling system was developed to determine rosiglitazone and glucose concentration in the brain and blood of gerbils subjected to treatment with rosiglitazone (3.0 mg kg(-1), i.p.). The results showed the limit of detection was 0.04 μg L(-1) and the correlation coefficient was 0.9997 for the determination of rosiglitazone in the brain. The mean parameters, maximum drug concentration (C(max)) and the area under the concentration-time curve from time zero to time infinity (AUC(inf)), following rosiglitazone administration were 1.06±0.28 μg L(-1) and 296.82±44.67 μg min L(-1), respectively. The time to peak concentration (C(max) or T(max)) of rosiglitazone occurred at 105±17.10 min, and the mean elimination half-life (t(1/2)) from brain was 190.81±85.18 min after administration of rosiglitazone. The brain glucose levels decreased to 71% of the basal levels in the rosiglitazone-treated group when compared with those in the control (p<0.01). Treatment with rosiglitazone decreased blood glucose levels to 80% at 1h after pretreatment of rosiglitazone (p<0.05). In addition, pretreatment with rosiglitazone significantly reduced the cerebral infarct volume compared with that of the control group. These findings suggest that this method may be useful for simultaneous and continuous determination of rosiglitazone and glucose concentrations in brain and plasma. Rosiglitazone was effective at penetrating the blood-brain barrier as evidenced by the rapid appearance of rosiglitazone in the brain, and rosiglitazone may contribute to a reduction in the extent of injuries related to cerebral ischemic stroke via its hypoglycemic effect.     

Biopharmaceutics of Didanosine in Humans and in a Model for Acid-Labile Drugs,the Pentagastrin-Pretreated Dog

Didanosine is a purine nucleoside analogue approved for the treatment of human immunodeficiency virus infection. It is extremely unstable at pH values less than 3 and requires protection against gastric acid-induced hydrolysis. Beagle dogs pretreated with pentagastrin, an analogue of gastrin that reproducibly stimulates gastric acid secretion, have been used to screen different didanosine formulations. The absolute bioavailability of didanosine from a saline solution decreased from approximately 43% in untreated dogs to 8% after pretreatment with pentagastrin. Administration of buffered solution of didanosine to untreated and pretreated dogs yielded bio-availability estimates of 37 and 30%, respectively. In humans, the bioavailability from a similar buffered solution was approximately 40%. Pentagastrin-pretreated dogs were used to evaluate four new products relative to a citrate-phosphate buffer sachet, the formulation selected for large-scale clinical trials in humans. Two of these new formulations, a chewable tablet and an antacid suspension, were more bioavailable then the reference sachet. This also proved to be true in man, necessitating an adjustment in the dose of didanosine when administered as the chewable tablet. Dogs pretreated with pentagastrin accurately predicted the improved bioavailability of new didanosine formulations prior to clinical use. This animal model may be helpful in evaluating the biopharmaceutics of other acid-labile drugs.     

Influence of shear intensity and total shear on properties of blends and tablets of lactose and cellulose lubricated with magnesium stearate

A new technique to quantify the effects of shear intensity and total shear on the homogeneity, flowability and bulk density of a lubricated free-flowing pharmaceutical blend and on properties of resulting tablets is presented. A modified Couette cylindrical cell with uniformly spaced pins is used to create a uniform shear environment. The range of lubricant concentrations explored is 0-2% (on a mass basis). Sheared blends are used to produce tablets in the Presster (a simulator of an actual tablet press), allowing us to correlate the shear history of the blend (shear intensity and total shear) with the crushing hardness of tablets. The results show that the larger the total shear, the more homogeneous the blend. Bulk density increases with total shear until reaching a distinctive plateau. Results also indicate that high total shear affects the blend flow properties. For tablets, crushing hardness decreases as concentration of lubricant and total shear increase. Interestingly, and unexpectedly, under constant total shear, shear intensity affects the crushing hardness of tablets only slightly.     

Nanoparticles in drug delivery: mechanism of action,formulation and clinical application towards reduction in drug-associated nephrotoxicity

Introduction: Over the past few decades, nanoparticles (NPs) have gained immeasurable interest in the field of drug delivery. Various NP formulations have been disseminated in drug development in an attempt to increase efficacy, safety and tolerability of incorporated drugs. In this context, NP formulations that increase solubility, control release, and/or affect the in vivo disposition of drugs, were developed to improve the pharmacokinetic and pharmacodynamic properties of encapsulated drugs.

Areas covered: In this article, important properties related to NP function such as particle size, surface charge and shape are disseminated. Also, the current understanding of how NP characteristics affect particle uptake and targeted delivery is elucidated. Selected NP systems currently used in delivery of drugs in biological systems and their production methods are discussed as well. Emphasis is placed on current NP formulations that are shown to reduce drug-induced adverse renal complications.

Expert opinion: Formulation designs utilizing NP-encapsulated drugs offer alternative pharmacotherapy options with improved safety profiles for current and emerging drugs. NPs have been shown to increase the therapeutic index of several entrapped drugs mostly by decreasing drug localization and side effects on organs. Recent studies on NP-encapsulated chemotherapeutic and antibiotic medications show enhanced therapeutic outcomes by altering drug degradation, increasing systemic circulation and/or enhancing cell specific targeting. They may also reduce the distribution of encapsulated drugs into the kidneys and attenuate drug-associated adverse renal complications. The usefulness of NP formulation in reducing the nephrotoxicity of nonsteroidal anti-inflammatory drugs is an underexplored territory that deserves more attention.     

高效液相色谱法测定血浆中更昔洛韦及其生物等效性

目的建立高效液相色谱法测定血浆中更昔洛韦浓度,并研究其生物等效性。方法18名受试者随机等分成2组,先后单剂量口服受试制剂或参比制剂后,采用HPLC法测定血药浓度,计算药物动力学参数并进行生物等效性判定。结果单次服用1 000 mg受试制剂或参比制剂后的药物动力学参数AUC0~24分别为(2 919.2±1426.9)、(3 018.3±1 663.4)ng.h.mL-1,AUC0~∞分别为(3 217.9±1 575.1)、(3 359.5±1 720.5)ng.h.mL-1,tmax分别为(1.5±0.5)、(1.7±0.6)h,Cmax分别为(482.6±212.1)、(515.9±228.0)ng.mL-1,t1/2分别为(7.70±1.56)、(7.77±3.34)h。受试制剂对参比制剂的相对生物利用度为100.1%±15.3%。2种制剂的药物动力学参数无明显差异。结论HPLC法能快速、准确地测定人血浆中的更昔洛韦,受试制剂与参比制剂具有生物等效性。