双氯芬酸钠缓释栓相对生物利用度研究

目的 :研究兔直肠给予双氯芬酸钠缓释栓的相对生物利用度 ,为临床合理用药提供参考。方法 :多剂量给予普通栓和缓释栓 ,采用反相高效液相色谱法测定血浆中双氯芬酸钠的浓度。结果 :兔直肠给予双氯芬酸钠缓释栓的药动学参数为 :AUC 71.8μg·mL 1 ·h ;t1 2 (ka) 0 .19h ;t1 2 (ke) 1.4h ;tmax0 .5 4h ;Cmax2 7.6μg·mL 1 ;CL 0 .76L 1 ·kg 1 ·h 1 ;Ka 5 .12h 1 ;Ke0 .5 6h 1 。普通栓在兔体内的药动学参数为 :AUC 61.5 8μg·mL 1 ·h ;t1 2 (ka) 0 .15h ;t1 2 (ke) 1.0 9h;tmax0 .49h ;Cmax2 9.3 8μg·mL 1 ;CL 0 .82L 1 ·kg 1 ·h 1 ;Ka8.90h 1 ;Ke0 .67h 1 。求算得双氯芬酸钠缓释栓的相对生物利用度 116.5 % ,对两种制剂的药动学参数进行双、单侧t检验 ,均差异无显著性 (P >0 .0 5 ) ,缓释栓的Cmax低于普通栓 ,tmax及t1 2 (ka) 均长于普通栓。表明该栓剂在体内吸收与代谢较慢 ,具有缓释长效的特点。结论 :缓释栓的AUC比普通栓的AUC大 ,并具有达峰时间长 ,在体内时间长的特点 ,具有长效、缓释作用。且缓释栓与普通栓具有生物等效性。     

布洛芬缓释混悬液空腹和餐后给药的人体生物等效性研究

目的:研究健康受试者空腹和餐后两种状态下单剂量口服布洛芬缓释混悬液受试制剂与参比制剂的生物等效性。方法:本研究包括两个随机、开放、双周期、单剂量给药试验,各入组24名健康受试者,分别空腹和餐后单剂量交叉口服600 mg(20 ml)布洛芬混悬液受试制剂与参比制剂,采用液相色谱-串联质谱(LC-MS/MS)法测定给药后血浆中布洛芬的浓度。结果:空腹给药条件下受试制剂与参比制剂的主要药动学参数中t1/2分别为(4.27±1.42)和(3.87±1.03)h;tmax分别为(3.42±0.72)和(3.29±0.93)h;cmax分别为(27.4±4.33)和(28.2±4.65)μg/ml;AUC0-t分别为(167±30.1)和(172±28.8)μg·h/ml;受试制剂的相对生物利用度为(97.4±9.7)%。餐后给药条件下受试制剂与参比制剂的主要药动学参数中t1/2分别为(2.53±0.46)和(2.64±0.53)h;tmax分别为(3.63±0.99)和(3.44±1.15)h;cmax分别为(25.0±4.12)和(27.0±4.60)μg/ml;AUC0-t分别为(172±33.4)和(184±30.2)μg·h/ml;受试制剂的相对生物利用度为(93.1±5.7)%。两种给药条件下的受试制剂与参比制剂AUC0-t和cmax几何均值比的90%置信区间(CI)均落在80%~125%之间。结论:布洛芬缓释混悬液受试制剂与参比制剂在空腹和餐后两种状态下均具有生物等效性。     

右旋布洛芬缓释胶囊在比格犬体内的药物动力学

目的建立一种快速、专属的HPLC UV法用于测定比格犬血浆中右旋布洛芬的浓度 ,应用本法对右旋布洛芬缓释胶囊在比格犬体内的药物动力学行为进行研究。方法 8只比格犬采用双周期交叉试验设计 ,分别口服给予右旋布洛芬缓释胶囊 (受试制剂 )及清芬片 (右旋布洛芬片 ,参比制剂 )后按时间点采集血样进行分析 ,绘制血药质量浓度 时间曲线 ,计算相关药动学参数。结果经统计分析 ,两种制剂间药动学参数AUC0 -t、AUC0 -∞ 无显著性差异 ,受试制剂峰质量浓度 ρmax低于参比制剂 ,tmax显著增大。结论受试制剂右旋布洛芬缓释胶囊具备了一定的缓释特征     

酮洛芬巴布贴片在兔体内的相对生物利用度研究

目的 研究酮洛芬巴布药在兔体内药动学和相对生物利用度。方法 按设计采集12 h内动态血浆标本，以高效液相色谱（HPLC）法测定酮洛芬血浆浓度，以一室模型计算酮洛芬巴布药和贴片在兔体内的药动学参数和相对生物利用度。结果 两制剂兔体内药动学过程符合一室模型。巴布药和贴片的主要药动学参数分别是AUC: (1 302.71±358.78)和(1175.68±364.35) μg·min·mL^-1; t_{1/2 (Ka)}：（31.95±18.37）和(32.89±11.13) min；t_{1/2 (Ke)}：(448.23±241.30)和(318.20±124.45) min；t_max:( 123.59±52.04)和(117.36±34.86) min；C_max:( 2.38±1.31)和(2.22±1.27) μg·mL^-1。结论 酮洛芬巴布贴片具有与上市贴片相似的生物学效应。     

国产右旋布洛芬缓释胶囊在大鼠体内的药动学及生物利用度研究

目的 考察自制和市售右旋布洛芬缓释胶囊在大鼠体内的药动学性质与生物等效性.方法建立反相高效液相色谱法,测定右旋布洛芬在血浆中的浓度,进行药动学和相对生物利用度研究.结果自制和市售右旋布洛芬缓释胶囊的主要药动学参数C_max分别为(1 173.87±281.68),(1 186.06±268.79) μg.mL^-1;AUC_(0-t)分别为(4 276.53±578.59),(4 489.83±645.73) mg.L^-1.h;AUC_(0-∞)分别为(5 095.58±683.82),(5 466.37±753.35) mg.L^-1.h;t_max分别为(1.33±0.26),(1.58±0.49) h;各参数间比较差异无统计学意义(P>0.05),以AUC_(0-∞)计算自制右旋布洛芬缓释胶囊的相对生物利用度为(93.2±12.5)%.结论自制右旋布洛芬缓释胶囊与市售制剂之间生物等效.     

布洛芬混悬液与片剂人体生物等效性研究

目的 :通过对布洛芬混悬液人体内药物动力学及生物利用度研究 ,评价该制剂与片剂的生物等效性。方法 :采用高效液相色谱法测定 18名健康男性志愿者自身交叉单剂量口服布洛芬混悬液和布洛芬片剂 4 0 0mg的经时血药浓度。药 时曲线数据经 3P87药物动力学计算程序处理 ,计算主要药物动力学参数以及受试制剂的生物利用度 ,同时评价 2种制剂的生物等效性。结果 :受试制剂和参比制剂的吸收速率常数 (Ka)分别为 (1 6 5± 1 4 6 )h-1和 (0 70± 0 2 5 )h-1;消除半衰期 (T1/ 2 )分别为 (1 89± 0 32 )h和 (1 92± 0 38)h ;峰浓度 (cmax)分别为 (5 2 6 2± 14 2 1) μg·mL-1和 (42 4 3± 10 6 2 ) μg·mL-1;达峰时间 (tmax)分别为 (1 5 5± 0 70 )h和 (2 6 8± 0 86 )h ;药 时曲线下面积 (AUC0→∞)分别为 (2 4 2 0 3± 35 70 ) μg·h·mL-1和 (2 37 0 4± 39 6 3) μg·h·mL-1;受试制剂的生物利用度 (F)为 (10 2 81± 11 4 5 ) %。经统计学处理 ,2种制剂的Ka ,cmax,tmax有显著性差异 (P <0 0 5 ) ;布洛芬混悬液吸收迅速 ,T1/ 2 ,AUC0→∞ 无显著性差异 (P >0 0 5 )。结论 :布洛芬混悬液与片剂具有生物等效性     

布洛芬缓释片的人体生物等效性研究

目的:研究布洛芬缓释片在健康人体内的药动学及其相对生物利用度,以评价其与布洛芬缓释胶囊的生物等效性。方法:18名男性志愿者,随机分为2组,分别口服布洛芬缓释片(受试制剂)与布洛芬缓释胶囊(参比制剂)后,采用高效液相色谱法测定血药浓度,用3p97药动学程序拟合,计算药动学参数。结果:受试制剂与参比制剂Cmax分别为(25.43±0.78)、(26.87±0.66)μg·mL-1,tmax分别为(3.67±0.52)、(3.83±0.75)h,AUC0~24分别为(181.20±5.12)、(187.58±5.29)μg·h·mL-1,AUC0~∞分别为(184.34±5.35)、(191.19±4.87)μg·h·mL-1,MRT分别为(6.51±0.73)、(6.80±0.48)h;受试制剂的相对生物利用度为103.7%。结论:与参比制剂比,布洛芬缓释片有较好的缓释效果。     

甲磺酸酚妥拉明栓剂兔体内相对生物利用度和阴茎组织中药物浓度

目的:研究甲磺酸酚妥拉明栓剂在兔体内的相对生物利用度和阴茎组织中药物浓度。方法:单剂量栓剂和片剂口服给药,采用高效液相色谱法测定血浆和阴茎组织中甲磺酸酚妥拉明的浓度。结果:栓剂和片剂给药的药动学过程均为一室模型,主要药动学参数分别为:AUC:(58.8±12.6)μg.h.L-1和(55.7±5.0)μg.h.L-1;t1/2(Ka):(0.17±0.029)h和(0.18±0.04)h;t1/2(Ke):(5.1±2.0)h和(4.6±1.7)h;Tmax:(0.79±0.14)h和(0.81±0.08);Cmax:(7.7±0.5)μg.L-1和(8.1±0.4)μg.L-1。根据两制剂AUC求算得甲磺酸酚妥拉明栓的相对生物利用度为105.43%,对两种制剂的药动学各参数进行双、单侧t检验,差异均无显著性(P>0.05)。两制剂具有生物学等效性。甲磺酸酚妥拉明栓和片的阴茎组织中药物质量浓度分别为4.23ng.g-1和2.73ng.g-1,两者差异有显著性(P<0.01)。结论:本品具有直肠给药阴茎局部药物浓度高于口服给药浓度的特点。     

布洛芬混悬液的研制及其生物利用度

通过处方、工艺筛选 ,以羧甲纤维素为助悬剂、蔗糖和甘露醇为矫味剂制备布洛芬混悬液 ,并在 10名健康志愿者中进行生物利用度研究。采用 HPL C法测定人血清中布洛芬浓度 ,并与市售布洛芬片进行比较。结果显示 ,单剂量口服 30 0 mg布洛芬混悬液和片剂的药动学参数分别为 tmax(0 .790± 0 .36 0 ) h和 (4.0 2 4± 0 .819) h;cmax(2 2 .2 8± 3.6 8) μg/m l和 (2 0 .0 4± 3.370 ) μg/ml;t1 / 2 (2 .0 2 6± 0 .2 70 ) h和 (2 .0 2 6± 0 .2 6 5 ) h。混悬液的相对生物利用度为(91.4 6± 10 .5 9) % ,与布洛芬片相比无显著性差异。     

格列齐特缓释片的人体生物等效性

目的:进行试验制剂格列齐特缓释片和市售参比制剂达美康缓释片的人体生物等效性研究,评价缓释制剂的释放特点、稳态血浓度和波动度。方法:采用高效液相色谱法测定单剂和多剂交叉给药格列齐特经时血浓度,计算其药动学参数,并进行方差分析和双单侧t检验。结果:试验制剂和参比制剂单剂口服给药格列齐特半衰期(t1/2)为(24.2±2.5)h和(23.8±3.2)h,血浓度峰值(Cmax)为(1.9±0.6)mg.L-1和(2.2±0.5)mg.L-1,达峰时间(tmax)为(6.9±1.0)h和(6.4±1.0)h,药时曲线下面积(AUC0-72)为(54.7±14.2)mg.h.L-1和(58.8±16.4)mg.h.L-1,相对生物利用度(F)为(93.7±8.4)%。试验制剂和参比制剂多剂给药格列齐特AUCSS为(59.7±24.4)mg.h.L-1和(62.6±25.5)mg.h.L-1,Cmax为(3.4±1.3)mg.L-1和(3.8±1.4)mg.L-1,Cmin为(1.89±0.8)mg.L-1和(1.6±0.9)mg.L-1,波动系数(DF)为(61.3±17.9)%和(87.5±21.5)%,生物利用度F为(95.9±11.2)%。结论:格列齐特缓释制剂单剂和多剂双周期双交叉口服给药,3因素方差分析和双单侧t检验,格列齐特主要药动学参数符合生物等效的假设,为生物等效制剂。与市售参比制剂比,试验制剂缓释、波动度小的特征明显。     

The effect of colestipol and cholestyramine on the systemic clearance of intravenous ibuprofen in rabbits

Abstract— The effect of oral administration of the non-absorbable anion-exchange resins cholestyramine and colestipol on the systemic clearance and other pharmacokinetic parameters of intravenously administered ibuprofen (25 mg kg^?1) was studied in rabbits. Single doses of colestipol hydrochloride (0·4 g kg^?1) or cholestyramine (0·17 g kg^?1) were given 30 min before ibuprofen administration. In cholestyramine-treated rabbits a significant reduction in ibuprofen plasma concentration was observed compared with both control (water only) and colestipol-treated rabbits. Cholestyramine treatment resulted in a significant decrease in the terminal elimination half-life and the mean residence time. Furthermore, a 31% increase in the systemic clearance and 23% decrease in the area under the plasma concentration-time curve were also observed in cholestyramine-treated rabbits. Colestipol treatment did not change these parameters. The volume of distribution parameters (Vd_ss and Vd_area) did not change following either treatment. The changes in the pharmacokinetic parameters are compatible with an acceleration of ibuprofen elimination induced by oral administration of cholestyramine and not by colestipol. This effect is thought to be due to augmentation of net biliary excretion through enteric binding.     

精氨洛芬片剂与颗粒剂在健康受试者体内的生物等效性

目的 研究精氨洛芬(非甾体抗炎药)片剂与颗粒剂在中国健康志愿者体内的生物等效性.方法 20名健康男性受试者分别随机交叉口服精氨洛芬片(试验制剂)及其颗粒(参比制剂)0.4 g,用HPLC-UV法测定给药后不同时间点的血浆布洛芬浓度;用DAS程序对试验数据进行统计处理,评价2种制剂的生物等效性.结果 试验制剂和参比制剂的药代动力学参数如下:Cmax分别为(50.60±9.12)、(50.53±8.58)nag·L-1,tmax分别为(0.51±0.20)、(0.34±0.11)h,AUC0～t分别为(118.63±21.42)、(115.75±20.23)mg·h·L-1,AUC0～∞分别为(121.18±22.18)、(118.55±21.83)mg·h·L-1.试验制剂与参比制剂AUC0-t之比和Cmax之比的90%可信区间分别为97.5%～107.6%和93.3%～107.2%.结论 试验制剂和参比制剂吸收程度等效(AUC0-t,AUC0-∞和Cmax均生物等效性);但吸收速度不等效(tmax不等效).     

超临界流体快速膨胀法制备物质微粉Ⅱ布洛芬微粉混悬剂质量评价

考察了由超临界流体快速膨胀法制得的布洛芬微粉制备的混悬剂的流体力学特征，并与以原料药及超细气流粉碎法制得的布洛芬微粉为原料制备的混悬剂作了比较。     

Dissolution of ibuprofen enantiomers from coprecipitates and suspensions containing chiral excipients

The purpose of this research was to evaluate the stereospecific interaction of ibuprofen with chiral excipients such as hydroxypropyl-beta-cyclodextrin (HPCD), tartaric acid, sucrose, hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), and a nonchiral excipient, citric acid. Coprecipitates of ibuprofen were prepared in molar ratios ranging between 1:0.5 and 1:10 by a solvent evaporation method and characterized using x-ray diffraction, Fourier-transform infrared (FTIR) spectroscopy, and dissolution testing. Phase solubility studies of ibuprofen were carried out by adding excess amount of ibuprofen to aqueous excipient solutions of varying concentrations. Interaction was studied in suspensions of ibuprofen with HPMC, MC, and sucrose stored at room temperature and 60 degrees C for 12 weeks. Solubility of ibuprofen in HPCD solutions increased 10-fold, whereas solubility decreased in the tartaric and citric acid solutions, a result of decreased pH with increased amount of the acids in which ibuprofen (pKa 4.8) is less soluble. Phase solubility diagrams of ibuprofen in aqueous HPCD, citric acid, and tartaric acid solutions showed no stereospecific differences in solubility of the two enantiomers. X-ray diffraction studies showed that ibuprofen exists in a crystalline form at low ibuprofen-to-excipient ratios, whereas at the higher ratios, it exists in an amorphous form. FTIR spectroscopy for HPCD coprecipitates showed a shift of the carbonyl stretching band of ibuprofen to a higher wavelength with a markedly decreased intensity, probably because of a breakdown in the intermolecular hydrogen bonding with ibuprofen and restriction of the drug molecule in the HPCD cavity, respectively. Dissolution profiles of the coprecipitates demonstrated higher dissolution rates than those of pure ibuprofen. The presence of chiral excipients did not appear to cause stereoselective release of the drug from the coprecipitates and the suspensions.     

A comparative study of top-down and bottom-up approaches for the preparation of micro/nanosuspensions

Nano-sizing offers a promising method for the formulation of poorly aqueous soluble compounds. Nanosuspensions can be prepared by top-down or bottom-up approaches. The different conditions encountered in these two approaches can greatly affect nanosuspension characteristics. In this study, milling via microfluidization and precipitation via sonication were compared to study their effects on the formation and stability of ibuprofen nanosuspensions. Various stabilizers (SLS, PVP K-30, Pluronic F-68 and F-127, Tween 80 and different hydroxypropyl methylcelluloses (HPMCs)) were evaluated. Both processes resulted in a similar trend in the initial particle size and comparable short-term physical stability of suspensions. Of all the stabilizers investigated, the HPMCs were the most effective both in terms of particle size reduction and short-term physical stability. Differences in stabilizer efficacy were observed between the two processing methods. The initial particle size of the suspensions prepared using microfluidization correlated with the solubility of ibuprofen in the respective stabilizer solutions. Whereas, the initial particle size of suspensions prepared using precipitation under sonication correlated with the HLB values of the stabilizers. The solubility of ibuprofen in the stabilizer solution also played a significant role in the increase in particle size on storage, indicating Ostwald ripening.     

Prevention of postsurgical peritoneal adhesion formation by intraperitoneal administration of ibuprofen

Previously, we reported a reduction in the formation of post-surgical peritoneal adhesions accompanying the use of systemically administered ibuprofen in validated animal models. Since the use of systemic ibuprofen requires high doses, we evaluated intraperitoneal drug delivery to assess the effects of locally administered low doses of ibuprofen on adhesion formation. Adhesion formation was evaluated after (a) parietal peritoneal excision, (b) abrasion of large bowel serosal, and (c) both (a + b) performed together. Adhesions formed in 2/15 rabbits with parietal peritoneal excision only, 3/15 with serosal abrasion only, and 11/15 with both procedures performed in the same rabbit. To further validate the parietal peritoneal excision + adjacent serosal abrasion technique for adhesion induction, a second group of 23 rabbits was similarly treated; 20/23 were found to have adhesions. The minimum dose of ibuprofen delivered into the intraperitoneal cavity via Alzet pump which reduced adhesions was 5 μg/10 μl/5 cm² test site/hr. No more than 4–5 days of postoperative treatment were required to achieve a significant reduction in adhesion formation. In the 2-kg rabbits used here that would provide a total daily dose of 60 μg/kg/day. The minimum effective dose reported by this laboratory via systemic administration of ibuprofen for reduction of postsurgical peritoneal adhesions using a similar model was 35,000 μg/kg/day. The potential utility of these findings is enhanced by the ongoing development of biodegradable drug delivery systems which can administer ibuprofen within the peritoneal cavity.     

Clinical pharmacology of predisintegrated ibuprofen 800 mg tablets: an endoscopic and pharmacokinetic study

Thirty-five healthy adults were randomized to receive either: (1) ibuprofen 800 mg tablets; (2) ibuprofen 800 mg aqueous suspension; (3) ibuprofen 800 mg orange juice suspension; or (3) 325 mg aspirin tablets. All treatments were tid for 7 days. Pharmacokinetic sampling was conducted on days 1, 4 and 8. Gastroduodenoscopy was performed on days 1 and 8. Side effects and safety laboratory tests were monitored throughout the study. On day 8 the aspirin group showed significantly more gastric irritation than all of the ibuprofen groups (P less than .005). Both ibuprofen suspension groups showed more gastric irritation than the ibuprofen tablet group (P less than .1). The duodenal scores did not differ among the treatment groups. The aspirin group experienced a higher rate of tinnitus and abdominal pain. The rate and extent of absorption of the ibuprofen suspensions were significantly less than that of the tablets. These data suggest that the taking of ibuprofen as an extemporaneous suspension is therapeutically inferior to ibuprofen tablets and therefore should be discouraged.     

Comparative study of anti-inflammatory activity of some branded generic and generic non-steroidal anti-inflammatory drugs

Generic drugs play a very important role in health care. A study was undertaken to ascertain the equality or inequality between generics and branded generics. NSAIDs are the most commonly used drugs. So these drugs were chosen for the study. Selected branded generic and generic products of ibuprofen, nimesulide, and diclofenac sodium were tested by oral administration of their suspensions to different groups of rats. Freshly prepared drug suspensions equivalent to doses of 40, 10, and 5?mg/kg of ibuprofen, nimesulide, and diclofenac sodium, respectively, were administered orally to the rats and anti-inflammatory activity was measured by the carrageenan-induced rat paw edema model employing Zeitlin’s apparatus to measure the paw thickness. Statistical analysis by t-test, of the activity at the point of maximum difference indicated that with respect to anti-inflammatory activity generic ibuprofen and generic diclofenac sodium are better than branded generic ibuprofen and branded generic diclofenac sodium, respectively, and generic nimesulide is similar to branded generic nimesulide. All the products studied meet the Pharmacopoeial requirements. Hence it may be concluded that branded generic and generic NSAIDs, tested in this study, are of the same efficacy and inter-changeability among branded generics, and switching between branded generics and generics would not result in any difference in efficacy.     

Formulation and evaluation of reconstitutable suspensions containing ibuprofen-loaded Eudragit microspheres

The objective of this work was to develop and evaluate reconstitutable suspensions of ibuprofen-loaded microspheres prepared with an acrylic polymer (Eudragit RS-PM). The microspheres were prepared by the quasi-emulsion solvent diffusion technique. To prepare reconstitutable suspension formulation, the microspheres used had a mean particle size of 316.6 microm and 99.8% loading efficiency. Xanthan gum was chosen as the suspending agent for the suspension formulations. D-sorbitol was used to impart palatability of suspensions. The amount of D-sorbitol affected sedimentation volume and redispersibility properties of suspensions. The highest improving effect was shown with 20.0% and 25.0% of D-sorbitol concentrations. It was observed that dispersion media of suspensions showed non-Newtonian flow characteristics. To ensure minimum drug leakage from the microspheres into the suspension, the pH was buffered at 3.60 using citrate buffer. The ibuprofen content calculated from the suspended microspheres was consistent with that from microspheres alone. This result indicated that no leakage of drug occurred from the microspheres in the suspension on storage. Moreover, the same release rate of ibuprofen from the microspheres suspension and microspheres alone indicated that the suspension medium studied did not affect the property of drug release. This study suggested that stable suspensions of ibuprofen-loaded microspheres could be formulated with 0.6% w/v xanthan gum by the addition of 20% w/v D-sorbitol.     

Stereoselective pharmacokinetics of ibuprofen and its lysinate from suppositories in rabbits

Studies were performed on the effect of ibuprofen racemate ionisation extent on the pharmacokinetics of its enantiomers following administration in suppositories to rabbits. The suppositories, containing 146.3 mg ibuprofen in acidic form (IBP) or 250 mg ibuprofen lysinate (IBPL), equivalent to the above IBP dose, were prepared using lipophilic Witepsol H-15 as a base and administered to rabbits in a crossover design. Compared with IBP, administration of IBPL was followed by faster absorption and elimination of R and S enantiomers. However, significant differences at alpha=0.05 were observed only at the stage of elimination. AUC was markedly higher following administration of suppositories containing IBP than following suppositories with IBPL and this pertained to both R and S enantiomers. Evident inversion of R into S form was noted 30 min following IBPL administration and 1 h after IBP administration. Ionisation extent only insignificantly affected the scope of chiral inversion of ibuprofen R into S form (AUC(S-IBP)/AUC(R-IBP)=1.66, AUC(S-IBPL)/AUC(R-IBPL)=1.57). No presystemic inversion of R into S was observed in rabbits following administration of IBP or IBPL in suppositories. IBP enantiomers were isolated from 0.5 ml serum using solid phase extraction in C(18) columns and were quantified by HPLC using the chiral Whelk O1 column and UV detector (lambda=264 nm).