头孢氨苄胶囊制剂人体生物等效性研究

目的:研究新仿制的头孢羟氨苄胶囊制剂与市场在售的同类制剂在健康人体内的生物等效性。方法:采用随机交叉试验设计,20名健康男性志愿者分别口服受试制剂与参比制剂500 mg,HPLC法测定血浆中头孢氨苄的浓度,用DAS 2.0软件计算药动学参数并进行生物等效性评价。结果:受试制剂和参比制剂两药的主要药代动力学参数,Cmax分别为(18.12±3.17)μg/ml和(21.28±3.77)μg/ml,Tmax分别为(1.09±0.37)h和(1.04±0.33)h,t1/2分别为(1.15±0.22)h和(1.14±0.20)h,AUC0-t分别为(35.43±5.39)μg h/ml和(37.27±4.76)μg h/ml,AUC0-∞分别为(36.68±6.06)μg h/ml和(38.62±5.48)μg h/ml,受试制剂的平均相对生物利用度为(96.50±7.2)%。结论:受试制剂和参比制剂具有良好的生物等效性。     

酮洛芬缓释片人体药动学和生物等效性研究

目的:评价受试酮洛芬缓释片与参比酮洛芬片的生物等效性。方法:采用反相高效液相色谱法测定24名健康男性志愿受试者交叉单剂量口服受试酮洛芬缓释片与参比酮洛芬片150mg后血浆中酮洛芬的浓度,用3p97程序进行数据处理。结果:口服受试和参比酮洛芬制荆后的AUC_(0-(?))分别是38.94±9.15μg·h·ml~(-1)、38.04±6.90μg·h·ml~(-1);AUC_(0-(?))分别是44.50±8.09μg·h·ml~(-1)、42.99±8.36μg·h·ml~(-1);T_(max)分别是3.87±0.55 h、1.96±0.60h;C_(max)分别是5.78±1.11μg·ml~(-1)、11.62±2.10μg·ml~(-1);t_(1/2)(Ke)分别是5.88±1.16h、1.70±1.40h。结论:受试酮洛芬缓释片与参比酮洛芬片具有生物等效性。     

雷诺嗪缓释片在比格犬体内的药代动力学

目的:研究雷诺嗪缓释片在比格犬体内的药物代谢动力学,并与参照制剂比较,为其是否具有缓释特征提供依据。方法:首先建立血浆中雷诺嗪浓度的液相色谱-串联质谱联用检测方法,并考察方法的专属性、准确度、日内日间精密度、回收率、线性范围等。采用随机对照试验设计,将12只比格犬随机分为A、B组,每组6只,分别服用1片雷诺嗪缓释片(500 mg/片)和1片参比制剂雷诺嗪片(500 mg/片),均于给药前和给药后不同时间点采集血样,用已建立的液质联用方法检测血样中雷诺嗪的血药浓度,计算2组比格犬的药代动力学参数。结果:受试组和参照组半衰期t1/2分别为13.3±8.3和2.36±0.92 h,峰浓度Cmax分别为923.9±340.5和3205±1314 ng/mL,达峰时间Tmax分别为1.6±0.38和0.88±0.14 h,曲线下面积AUC0~∞分别为6252.1±2860.3和9916±4305(ng·h)/mL,清除率Cl分别为11.3±9.8和6.39±3.95 L/(kg·h)。受试制剂雷诺嗪缓释片和参比制剂雷诺嗪片的药代特征和血药浓度-时间变化趋势明显不同,受试组血药浓度缓慢上升和下降,峰值较低;而参照组血药浓度峰值显著高于受试组,有明显的突释效应。结论:液质联用检测方法准确可靠,适合体内药代动力学研究;与参比制剂雷诺嗪片相比,受试制剂雷诺嗪缓释片符合缓释片的基本药代动力学特点。     

恩诺沙星在罗氏沼虾体内的药物代谢动力学

应用反相高效液相色谱法(RP-HPLC)研究了恩诺沙星在罗氏沼虾(Macrobrachiumrosenbergii)体内的药物代谢动力学。实验结果表明,恩诺沙星在血淋巴、肝胰腺、肌肉中的平均回收率分别为86.54%±2.39%、85.43%±2.75%、95.01%±1.99%,其代谢产物环丙沙星在血淋巴、肝胰腺、肌肉中的平均回收率分别为94.34%±8.30%、75.17%±5.42%、80.42%±1.67%;恩诺沙星及其代谢产物环丙沙星在三种组织中的平均日内精密度分别为3.39%±0.53%和3.92%±1.24%,而日间精密度分别为5.11%±1.73%和5.28%±2.10%。恩诺沙星、环丙沙星的最低检测限分别为0.02μg/ml和0.01μg/ml。罗氏沼虾以10mg/kg虾体重剂量单次肌肉注射给药后,血液中药物浓度即刻达到峰值,并迅速向组织中分布。实验数据经MCPKP药动学软件分析,恩诺沙星在血淋巴中的主要药物代谢动力学参数为:t1/2α为0.581h、t1/2β为69.315h、Vd/F为7.230L/kg、CL/F为0.035L/h.kg、K12为0.01/h、K21为0.005/h、AUC为291.898μg/ml.h、Tmax为0.083h、Cmax为6.293μg/ml;恩诺沙星在肝胰腺、肌肉组织中主要药动学参数:t1/2α为1.941h、0.000h;t1/2β为70.732h、59.456h;AUC为308.07μg/ml.h、217.039μg/ml.h。三种组织中均能检测到恩诺沙星的活性代谢产物环丙沙星,但含量均处于较低水平,药物浓度-时间数据经MCPKP药动学软件处理后,不能用开放性一室模型或二室模型拟合。     

HPLC-MS/MS法测定人血浆中草乌甲素的浓度及生物等效性研究(英文)

本文建立了一种快速、高灵敏的HPLC-MS/MS法用于检测人血浆中的草乌甲素浓度。血浆样品采用沃特斯HLB小柱进行固相萃取,汉邦C18色谱柱(150 mm×4.6 mm,5μm)进行分离,流动相为甲醇∶水(85∶15,v/v),水相含10 mmol/L的醋酸铵和0.1%的甲酸。采用ESI源和多反应监测(MRM)的方式进行检测,草乌甲素及内标的反应离子对分别为644.4/584.4和237.2/194.2,草乌甲素血药浓度在0.010～1.0 ng/mL范围内线性关系良好,最低定量限为0.010 ng/mL可以满足口服0.4 mg草乌甲素后血药浓度的检测,日内日间及质控样品精密度及准确度均在允许范围内。本检测方法被成功的应用在中国健康志愿者生物等效性研究中,20名志愿者口服0.4 mg草乌甲素试验制剂和参比制剂后主要药代动力学参数分别如下:Cmax(0.325±0.110),(0.323±0.115)ng/mL;AUC0-16(1.627±0.489),(1.732±0.556)ng.h/mL;AUC0-∞(1.730±0.498),(1.831±0.562)ng.h/mL;t1/2(4.26±0.95),(3.80±0.90)h;Tmax(1.34±0.54),(1.83±0.99)h。     

辛伐他汀在大鼠体内药动学性别差异的研究

目的:研究Wistar大鼠单次灌服辛伐他汀后体内药代动力学的性别差异。方法:利用高效液相色谱方法检测大鼠血浆中辛伐他汀浓度,采用非房室模型法计算各自药动学参数。结果:雌、雄大鼠体内Cmax分别为(144.66±22.31)ng·mL~(-1)和(165.91±52.50)ng·mL~(-1);t_(1/2)分别为(4.74±1.19)h和(14.98±6.64)h;AUC_(0-10)分别为(0.990±0.19)μg.h·mL~(-1)和(0.726±0.15)μg·h·mL~(-1);AUC0-∞分别为(1.62±0.47)μg·h·mL~(-1)和(2.19±0.62)μg·h·mL~(-1);MRT分别为(9.69±1.60)h和(23.08±8.89)h,经t-检验,雌、雄大鼠主要药动学参数t_(1/2)、AUC_(0-10)、MRT均有统计学显著性差异(p<0.01)。结论:辛伐他汀在大鼠体内的药代动力学存在明显的性别差异,辛伐他汀在雌性大鼠体内代谢较快。     

复方依那普利非洛地平缓释片在健康中国人体内的药动学特征

目的:研究复方依那普利非洛地平缓释片在健康中国人体内的药动学特征。方法:采用双交叉实验设计,将12名健康受试者随机分为2组,先接受第1周期低剂量给药,即分别单次口服受试制剂(复方依那普利非洛地平缓释片,每片含非洛地平5 mg和马来酸依那普利5 mg)1片和2种单方参比制剂(马来酸依那普利片,含马来酸依那普利5 mg;非洛地平缓释片,含非洛地平5 mg)各1片,然后分别每日口服受试制剂1片和2种单方参比制剂各1片,连续7 d。第1周期结束后,2组再交叉进行第2周期研究,给药方案同第1周期。随后进行高剂量研究,即2组所有受试者均单次口服受试制剂2片。采用液质联用法测定人血浆中非洛地平、依那普利及其活性代谢物依那普利拉的浓度,计算药动学参数并进行统计学分析。结果:单次低剂量给药研究中,受试者分别口服受试制剂与合用2种单方参比制剂所测得的非洛地平、依那普利和依那普利拉的各药动学参数均无显著差异(P>0.05);多次低剂量给药研究中,除口服受试制剂者的依那普利拉Tmax比口服参比制剂的受试者平均提前0.6 h左右(P<0.05)以外,其他药动学参数均无显著差异(P>0.05);单次低、高剂量给药的药动学数据显示:所有受试者血浆中非洛地平、依那普利和依那普利拉的AUC和Cmax均随给药剂量提高而增大,除接受高剂量受试制剂者的依那普利Tmax较接受低剂量的受试者平均延迟0.4 h左右(P<0.05)以外,两者间的其他药动学参数均无显著差异(P>0.05);各药动学参数在男性和女性受试者间无显著差异(P>0.05)。结论:该研究建立的人血浆中非洛地平、依那普利和依那普利拉的LC-MS测定方法的准确度、精密度、稳定性及线性关系等均符合生物样品的分析要求,适用于复方依那普利非洛地平缓释片人体药动学研究;口服受试制剂与同服2种单方参比制剂的体内药动学过程基本一致。     

特比萘芬和伊曲康唑联合应用对暗色孢科真菌的体外药敏试验研究

目的本试验探讨特比萘芬和伊曲康唑单独及联合应用对54株暗色孢科真菌的体外相互作用。方法应用美国国家临床和实验室标准研究所(CLSI)的M38-A方案。菌悬液终浓度为(0.4～5)×106CFU/ml,孵育温度35℃,培养时间5～7d。各药单独和联合应用时的MIC值均为与生长对照孔相比100%生长抑制的最低药物浓度;药物间相互作用用分数抑菌浓度(FIC值)表示;FIC<1认为有协同作用,1≤FIC<2认为有相加作用,FIC=2认为无相关性,FIC>2认为有拮抗作用。结果单独用药时特比萘芬在紧密着色霉、裴氏着色霉、卡氏支孢霉和疣状瓶霉组中MIC的几何均数分别为0.198μg/ml,0.372μg/ml,0.215μg/ml,0.456μg/ml,伊曲康唑在紧密着色霉、裴氏着色霉、卡氏支孢霉和疣状瓶霉组中MIC的几何均数分别为0.232μg/ml,0.323μg/ml,0.186μg/ml和0.315μg/ml。体外联合用药时二者MIC几何均数低于其单独应用时的MIC值。在54株受试菌中,联合用药时协同作用为29.6%(16/54),相加作用为68.5%(37/54),拮抗作用为1.9%(1/54)。结论特比萘芬和伊曲康唑联合应用时表现以协同和相加作用为主,很少菌株表现拮抗现象。     

妇宁康泡腾胶囊的药代动力学研究

目的研究妇宁康泡腾胶囊在家兔体内的药动学特点。方法用HPLC法测定甘草酸在家兔体内48 h血药浓度,采用3P87药动学程序计算药动学参数。结果主要药动学参数为t1/2=8.956 h,Tmax=8.27 h,Cmax=0.4544μg/ml,AUC=37.161。结论该制剂在家兔体内吸收代谢缓慢,其生物半衰期超过8 h。     

RP-HPLC法测定阿托伐他汀在新西兰兔体内的药代动力学

目的:研究阿托伐他汀片在新西兰兔体内的药代动力学.方法:18只成年健康雄性新西兰兔.随机分为正常对照组、10mg/kg·d阿托伐他汀片组与15 mg/kg·d阿托伐他汀片组,每组6只,采用RP-HPLC法测定血药浓度,计算药代动力学参数.结果:10mg/kg·d组与15 mg/kg·d组的主要药代动力学参数分别为:AUC0～t/μ g·L-1·h为(619.58±215.45)与(1138.34±422.32)、AUC0～∞/μ g·L-1·h为(655.68±242.83)与(1216.57±353.64)、Cmax/μ g·L-1为(455.81±168.52)和(896.53±168.5.8)、MRT0～t/h为(3.68±0.75)与(5.73±0.56)、MRT0～∞/h为(3.83±0.91)与(5.25±0.48)、Tmax/h为(2.51±0.82)与(3.68±0.33)、T1/2/h为(4.22±0.55)与(9.51±0.67).结论:RP-HPLC法适用于阿托伐他汀片动物药代动力学的研究.     

Stereospecific versus nonstereospecific assessments for the bioequivalence of two formulations of racemic chlorpheniramine

Chlorpheniramine (chlorphenamine, CPAM) is a racemic antihistaminic H1 drug containing two enantiomers. The aim of this study was to assess the bioequivalence of two formulations (reference and Vietnamese-tested formulation) of racemic chlorpheniramine combined with phenylpropanolamine in an open-labeled, randomized, crossover two-period study, after administration of 8 mg of racemic chlorpheniramine in 12 healthy Vietnamese subjects. First, dissolution of both formulations was tested in vitro according to USP requirements. Then the 12 subjects received both formulations after an overnight fast and a 7-day wash-out period. Plasma samples were collected up to 168 h. Plasma concentrations of total chlorpheniramine and its individual enantiomers were determined with a validated chiral HPLC method and pharmacokinetic parameters were estimated using model-independent analysis. For the reference formulation, Cmax and AUC values were higher for (+)S-chlorpheniramine ((+)S-CPAM) compared to (-)R-chlorpheniramine ((-)R-CPAM) (13.3 vs. 6.8 ng/ml and 409 vs. 222 ng/ml/h, respectively) while Clt/F and Vd/F were lower (9.8 vs. 17.6 l/h and 321 vs. 627 l, respectively). No difference was observed for Tmax, t(1/2), and MRT. Pharmacokinetic parameters were similar for the reference and the Vietnamese-tested formulation. Bioequivalence was assessed by Schuirmann test, as recommended by the current FDA and European Community criteria. Dissolution tests showed that both formulations were equivalent. A nonstereospecific, but not a stereospecific, approach indicated bioequivalence between the formulations.     

Bioequivalence of two fexofenadine formulations in healthy human volunteers after single oral administration

AIM: A randomized, two-way, crossover, bioequivalence study was conducted in 25 fasting, healthy, male volunteers to compare two brands of fexofenadine 180 mg tablets, FEXOFENADINE 180 mg Film Tablet (Drogsan A.S., Ankara, Turkey) as test and Telfast 180 mg Tablet (Aventis Pharma, Frankfurt am Main, Germany) as a reference product. METHOD: One tablet of either formulation was administered after 10 h of overnight fasting. After dosing, serial blood samples were collected during a period of 48 hours. Plasma samples were analysed for fexofenadine by a validated HPLC method. The pharmacokinetic parameters AUC(0-48), AUC(0-alpha), C(max), T(max), K(el), T(1/2), and CL were determined from plasma concentration-time profiles for both formulations and were compared statistically. RESULTS AND CONCLUSIONS: The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals (CI) fell within the acceptable range, satisfying the bioequivalence criteria of the FDA. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetics profiles and that Drogsan's Fexofenadine is equivalent to Telfast of Aventis Pharma, Frankfurt am Main, Germany.     

氯雷他定固体自乳化制剂的体外溶出及体内药动学研究

目的:研究氯雷他定固体自乳化制剂的体外溶出行为及其在比格犬体内的药物动力学。方法:采用HPLC方法测定氯雷他定固体自乳化制剂与市售片剂的体外溶出曲线;采用LC-MS/MS测定市售片剂和氯雷他定固体自乳化制剂在比格犬体内的血药浓度,考察氯雷他定固体自乳化制剂的相对生物利用度。结果:以0.1 mol·L-1盐酸溶液为溶出介质的体外溶出结果表明,氯雷他定固体自乳化胶囊与市售片剂30 min时均可以溶出80%以上;比格犬体内药物动力学研究结果表明,固体自乳化制剂比市售片剂最高血药浓度显著性增加(P0.05),Cmax=1.79μg·L-1,而市售片剂Cmax=0.67μg·L-1;AUC(0~t)提高了149%(P0.05)。结论:固体自乳化制剂可以显著提高氯雷他定的体内吸收。     

Bioequivalence of two brands of citalopram 40 mg tablets after single oral administration to healthy volunteers

A randomized, two-way, crossover, bioequivalence study was conducted in 26 fasting, healthy, male volunteers to compare two brands of citalopram 40 mg tablets, Citol (Abdi Ibrahim Ila? San. ve Tic A.S., Istanbul, Turkey) as a test and Cipramil (H. Lundbeck A/S, Copenhagen, Denmark) as a reference product. One tablet of either formulation was administered with low-carbonate water after 10 h of overnight fasting. After dosing, serial blood samples were collected during a period of 24 hours. Plasma samples were analysed for citalopram by a validated HPLC method. The pharmacokinetic parameters AUC0-24, AUC(0-alpha), Cmax, Tmax, K(el), T(1/2), and CL were determined from plasma concentration-time profiles for both formulations and were compared statistically to evaluate bioequivalence between the two brands of citalopram, using the statistical modules recommended by FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetics profiles and that Abdi Ibrahim's Citol is equivalent to Cipramil of H. Lundbeck, Copenhagen, Denmark.     

Tablet formulation containing meloxicam and beta-cyclodextrin: mechanical characterization and bioavailability evaluation

The purpose of this research was to evaluate beta-cyclodextrin (beta-CD) as a vehicle, either singly or in blends with lactose (spray-dried or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of beta-CD was investigated. The tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution studies. The effect of beta-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced 2-way crossover study. Phase-solubility studies indicated an A(L)-type diagram with inclusion complex of 1:1 molar ratio. The powder blends and granules of all formulations showed satisfactory flow properties, compressibility, and drug content. All tablet formulations prepared by direct compression or wet granulation showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of beta-CD in the formulations up to 30%. The mean pharmacokinetic parameters (C(max), K(e), and area under the curve [AUC](0-infinity)) were significantly increased in presence of beta-CD. These results suggest that beta-CD would facilitate the preparation of meloxicam tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between tablets prepared by direct compression and those prepared by wet granulation. Also, beta-CD is particularly useful for improving the oral bioavailablity of meloxicam.     

Comparative in vitro and in vivo evaluation of matrix,osmotic matrix,and osmotic pump tablets for controlled delivery of diclofenac sodium

The aim of this investigation was preparation and comparative evaluation of fabricated matrix (FM), osmotic matrix (OM), and osmotic pump (OP) tablets for controlled delivery of diclofenac sodium (DS). All formulations were evaluated for various physical parameters, and in vitro studies were performed on USP 24 dissolution apparatus II in pH 7.4 buffer and distilled water. In vivo studies were performed in 6 healthy human volunteers; the drug was assayed in plasma using HPLC, and results were compared with the performance of 2 commercial tablets of DS. Various pharmacokinetic parameters (ie, C_max, T_max, area under the curve [AUC_0–24], and mean residence time) and relative bioavailability were compared. All fabricated formulations showed more prolonged and controlled DS release compared with commercial tablets studied. The OM and OP tablets, however, performed better than the matrix tablets. The rate and extent of drug release from FM1 matrix tablets (single polymer) was significantly different from that of FM2 (admixed polymers). Type of porosigenic agents and osmogens also influenced the drug release. Analysis of in vitro data by regression coefficient analysis revealed zero-order release kinetics for OM and OP tablets, while FM tablets exhibited Higuchi kinetics. In vivo results indicated prolonged blood levels with delayed peak and improved bioavailability for fabricated tablets compared to commercial tablets. It was concluded that the osmotic matrix and osmotic pump tablets could provide more prolonged, controlled, and gastrointestinal environmental-independent DS release that may result in an improved therapeutic efficacy and patient compliance.     

Development of a sensitive high-performance thin-layer chromatography method for estimation of ranitidine in urine and its application for bioequivalence decision for ranitidine tablet formulations

A sensitive and simple HPTLC method was developed for estimation of ranitidine in human urine. The drug was extracted from urine after basification using dichloromethane. Dichloromethane extract was spotted on silica gel 60 F254 TLC plate and was developed in a mixture of ethyl acetate-methanol-ammonia (35:10:5 v/v) as the mobile phase and scanned at 320 nm. The RF value obtained for the drug was 0.67 +/- 0.03. The method was validated in terms of linearity (50-400 ng/spot), precision and accuracy. The average recovery of ranitidine from urine was 89.35%. The proposed method was applied to evaluate bioequivalence of two marketed ranitidine tablet formulations (150 mg, Formulation I and Formulation 2) using a crossover design by comparing urinary excretion data for unchanged ranitidine in six healthy volunteers. Various pharmacokinetic parameters like peak excretion rate [(dAU/dt)max], time for peak excretion rate (tmax), AUC0-24, AUC0-infinity, cumulative amount excreted were calculated for both formulations and subjected to statistical analysis. The relative bioavailability of Formulation 2 with respect to Formulation 1 was 93.76 and 95.31% on the basis of AUC0-24 and cumulative amount excreted, respectively. Statistical comparison of various pharmacokinetic parameters indicated that the two ranitidine tablet formulations are bioequivalent.     

Formulation, Release Characteristics and Bioavailability Study of Oral Monolithic Matrix Tablets Containing Carbamazepine

This study examined the release of carbamazepine (CBZ) from hydrophobic (Compritol 888 ATO) and hydrophilic-hydrophobic matrix combination (Compritol 888 ATO-hydroxpropyl methylcellulose, HPMC). Hydrophobic matrix tablets were prepared by hot fusion technique, while hydrophilic-hydrophobic matrix tablets were prepared by wet granulation technique. The properties of the compressed matrix tablets were determined according to the US Pharmacopoeia. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol CR 200). The bioavailability of CBZ formulations and Tegretol CR 200 were evaluated in beagle dogs. Carbamazepine presented a significant higher bioavailability from matrix tablets containing hydrophilic polymer (HPMC) than that obtained from Tegretol CR200. The average inter-subject plasma concentration variability CV% was the least with tablet containing hydrophilic polymer (HPMC) and was the highest with Tegretol CR 200 (33.8 and 54.1, respectively). Analysis of variance applied to log AUC(0-alpha) and log C(max) showed statistical significant differences among the three formulations (P < 0.05). Plotting the fraction of CBZ released in vitro and fraction absorbed showed a statistically significant relationship (R(2) = 0.935-0.975) for the three matrix tablets examined.     

<Emphasis Type="Italic">In Vivo</Emphasis> Assessment of Parenteral Formulations of Oligo(3-Hydroxybutyric Acid) Conjugates with the Model Compound Ibuprofen

Polymer-drug conjugates have gained significant attention as pro-drugs releasing an active substance as a result of enzymatic hydrolysis in physiological environment. In this study, a conjugate of 3-hydroxybutyric acid oligomers with a carboxylic acid group-bearing model drug (ibuprofen) was evaluated in vivo as a potential pro-drug for parenteral administration. Two different formulations, an oily solution and an o/w emulsion were prepared and administered intramuscularly (IM) to rabbits in a dose corresponding to 40 mg of ibuprofen/kilogramme. The concentration of ibuprofen in blood plasma was analysed by HPLC, following solid–phase extraction and using indometacin as internal standard (detection limit, 0.05 μg/ml). No significant differences in the pharmacokinetic parameters (C _max, T _max, AUC) were observed between the two tested formulations of the 3-hydroxybutyric acid conjugate. In comparison to the non-conjugated drug in oily solution, the relative bioavailability of ibuprofen conjugates from oily solution, and o/w emulsion was reduced to 17% and 10%, respectively. The 3-hydroxybutyric acid formulations released the active substance over a significantly extended period of time with ibuprofen still being detectable 24 h post-injection, whereas the free compound was almost completely eliminated as early as 6 h after administration. The conjugates remained in a muscle tissue for a prolonged time and can hence be considered as sustained release systems for carboxylic acid derivatives.