Comparative bioavailability study of doxycycline hyclate (equivalent to 100 mg doxycycline) capsules (doxycin vs vibramycin) for bioequivalence evaluation in healthy adult volunteers

This investigation was carried out to evaluate the bioavailability of a new capsule formulation of doxycycline (100 mg), doxycin, relative to the reference product, vibramycin (100 mg) capsules. The bioavailability was carried out in 24 healthy male volunteers who received a single dose (100 mg) of the test (A) and the reference (B) products after an overnight fast of at least 10 hours on 2 treatment days. The treatment periods were separated by a 2-week washout period. A randomized, balanced 2-way cross-over design was used. After dosing, serial blood samples were collected for a period of 48 hours. Plasma concentrations of doxycycline were analyzed by a sensitive and validated high-performance liquid chromatography assay. The pharmacokinetic parameters for doxycycline were determined using standard noncompartmental methods. The parameters AUC(0-t), AUC(0-infinity), Cmax, K(el), t(1/2) and Cmax/AUC(0-infinity) were analyzed statistically using log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pharmacokinetic parameters: AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were within the range 80-125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis of the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were 95.98-109.56%, 92.21 to 107.66%, 93.90-112.56%, and 96.0 to 106.91% respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) by the Schuirmann's two 1-sided t-tests. Therefore, the 2 formulations were considered to be bioequivalent.     

Comparative pharmacokinetics of 800 mg of acyclovir-containing Telviran and Zovirax tablets in healthy volunteers]

The authors performed a detailed comparative clinical and pharmacokinetic study with two 800 mg acyclovir containing tablets, namely the Telviran (EGIS Pharmaceuticals Ltd.) and the Zovirax (Wellcome Foundation Ltd.). The determination of the detailed pharmacokinetic parameters and the relative bioavailability was carried out on 24 healthy male volunteers in a two way, open, randomised, cross-over design study after single dose administration. The plasma concentration of acyclovir was determined by a newly developed and validated highly sensitive (LLOQ = 10 ng/ml) HPLC-UV bioanalytical method after sample preparation with RP-18 solid phase extraction method (SPE). The individual pharmacokinetic parameters calculated from the time-plasma concentration curve (tmax, Cmax, AUC0-infinity, AUC0-16, AUC0-t, AUC0-z, AUCRest, t beta 1/2, MRT, Cmax/AUC0-infinity) were compared with statistical methods (ANOVA, ANOVAlog, Confidence interval, Schuirmann, Wilcoxon tests). On the basis of the results of the statistical evaluation and the clinical study, there was no significant difference found between the two acyclovir containing preparations. The comparative pharmacokinetic study demonstrated, that the relative bioavailability of the 800 mg Telviran and Zovirax tablets are equivalent and the two products are bioequivalent.     

Comparative bioavailability study of two cefixime formulations administered orally in healthy male volunteers

The bioavailability of a new cefixime ((6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo-[4,2,0]-oct-2-ene-2-carboxylic acid, CAS 79350-37-1) tablet preparation (Loprax) was compared with that of a reference preparation of the drug in 24 healthy male volunteers. The trial was designed as an open, randomized, single-blind, two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg cefixime tablet as a test or reference formulation on 2 treatment days. The treatment periods were separated by a one-week washout period. The plasma concentrations of the drug were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-24h, AUC0-infinity, Cmax, t1/2, and Ke. The mean AUC0-infinity of cefixime was 45008.7 +/- 10989.9 and 45221.3 +/- 2155.7 n x h/ml for the test and reference formulation, respectively. The maximum plasma concentration (Cmax) of cefixime was on average 4746.9 +/- 1284 ng/ml for the test and 4726.3 +/- 1206.9 ng/ml for the reference product. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for test and reference tablets. The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of Cmax, AUC0-infinity and AUC0-24h of cefixime were in the bioequivalence range (94%-112%). Therefore, the two formulations were considered to be bioequivalent.     

Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers

This investigation was carried out to evaluate the bioavailability of a new suspension formulation of cefixime (100 mg/5 ml), Winex, relative to the reference product, Suprax (100 mg/5 ml) suspension. The bio-availability study was carried out in 24 healthy male volunteers who received a single oral dose (200 mg) of the test (A) and the reference (B) products on 2 treatment days after an overnight fast of at least 10 hours. The treatment periods were separated by a one-week washout period. A randomized, balanced two-way crossover design was used. After dosing, serial blood samples were collected over a period of 16 hours. Plasma concentrations of cefixime were analyzed using a sensitive high-performance liquid chromatographic assay. The pharmacokinetic parameters for cefixime were determined using standard non-compartmental method. The parameters AUC(0-t), AUC(0-infinity), Cmax, Kel, t1/2 and Cmax/AUC(0-infinity) were analyzed statistically using raw and log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pnfinity harmacokinetic parameters: AUC(0-t), AUC(0-infinity) Cmax, and Cmax/AUC(0-infinity) were within the range 80 - 125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax, and Cmax/AUC(0-infinity) were 88.93 - 107.10%, 89.09 - 107.11%, 89.63 - 108.58% and 96.85 - 105.29%, respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), and Cmax using the Schuirmann's two one-sided t-tests. Therefore, the two formulations were considered to be bioequivalent.     

Bioequivalence study of two losartan formulations administered orally in healthy male volunteers

The bioavailability of a new losartan preparation (2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt, CAS 114798-26-4) was compared with the reference preparation of the drug in 24 healthy male volunteers, aged between 19 and 32. The open, randomized, single-blind two-sequence, two-period crossover study design was performed. Under fasting conditions, each subject received a single oral dose of 100 mg losartan as a test or reference formulation. The plasma concentrations of losartan and its active metabolite were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-36h, AUC0-infinity, Cmax, t1/2, and Ke. Values of AUC0-infinity demonstrate nearly identical bioavailability of losartan from the examined formulations. The AUC0-infinity of losartan was 2019.92+/-1002.90 and 2028.58+/-837.45 ng x h/ml for the test and reference formulation, respectively. The AUC0-infinity of the metabolite was 10851.52+/-4438.66 and 11041.18 +/-5015.81 ng x h/ml for test and reference formulation, respectively. The maximum plasma concentration (Cmax) of losartan was 745.94+/-419.75 ng/ml for the test and 745.74+/-329.99 ng/ml for the reference product and the Cmax of the metabolite was 1805.77+/-765.39 and 1606.22 +/-977.22 ng/ml for the test and reference product, respectively. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for both losartan and its active metabolite. 90 % confidence limits calculated for Cmax and AUC from zero to infinity (AUC0-infinity) of losartan and its metabolite were included in the bioequivalence range (0.8-1.25 for AUC). This study shows that the test formulation is bioequivalent to the reference formulation for losartan and its main active metabolite.     

Pharmacokinetics and bioequivalence study of ranitidine film tablets in healthy male subjects

The aim of the present study was to compare the bioavailability of ranitidine (CAS 66357-35-5) from two different ranitidine hydrochloride (CAS 66357-59-3) film tablets (Ranitab 150 mg film tablets as test preparation and 150 mg film tablets of the originator product as reference preparation). The study was conducted according to an open-label, randomised two-period cross-over design with a wash-out phase of 9 days. Blood samples for pharmacokinetic profiling were taken up to 24 h post-dose, and ranitidine plasma concentrations were determined with a validated HPLC method with UV-detection. Maximum plasma concentrations (Cmax) of 461.8 ng/ml (test) and 450.6 ng/ ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC (0-infinity) of 2,488.6 ng . h/ml (test) and 2,528.8 ng . h/ml (reference) were calculated. The median tmax was 2.83 h (test) and 3.04 h (reference). Plasma elimination half-lives (t1/2) of 2.78 h (test) and 2.89 h (reference) were determined. Both primary target parameters AUC(0-infinity) and Cmax were tested parametrically by analysis of variance (ANOVA) and the 90% confidence intervals were between 91.93 %-106.98 % (AUC (0-infinity) and 92.34%-118.85% (Cmax). Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90 % confidence intervals of the T/R ratios of logarithmically transformed data were in the generally accepted range of 80 %-125 %.     

那格列奈分散片的人体生物等效性研究

目的 研究两种那格列奈片剂的人体相对生物利用度,评价其生物等效性.方法 选择20名健康男性志愿者,按照两制剂两周期的随机交叉试验设计,分别单剂量口服参比制剂(普通片)和受试制剂(分散片),剂量均为120mg,采用液相色谱-串联质谱(LC-MS/MS)法测定其血浆中那格列奈的质量浓度,用DAS1.0软件计算各药物代谢动力学参数并进行生物等效性统计分析.结果 受试制剂和参比制剂的主要药物代谢动力学参数,峰浓度(Cmax)分别为(9.1±1.7)μg/mL和(7.7±2.1)mg/L,达峰时间(tmax)分剐为(0.7±0.3)h和(1.9±1.1)h,0～10 h药时曲线下面积(AUC0-10)分别为(19.7±4.0)mg/(L·h)和(20.8±3.0)mg/(L·h),0～∞药时曲线下面积(AUC0-∞)分别为(20.0±4.1)μg/(mL·h)和(21.3±3.3)mg/(L·h),半衰期(t1/2)分别为(1.7±0.2)h和(1.6±0.2)h.两制剂的Cmaxtmax,AUC0-10均存在显著性差异.双单侧t检验结果表明,受试制剂Cmax的90%置信区间落在参比制剂的75%～133%范围内,AUC的90%置信区间均落在参比制剂的80%～125%范围内,相对生物利用度为(94.9±14.4)%.结论 两制剂具有生物等效性.     

Bioequivalence study of finasteride. Determination in human plasma by high-pressure liquid chromatography coupled to tandem mass spectrometry

Two different finasteride (CAS 98319-26-7) tablet formulations were evaluated for their relative bioavailability (Flaxin tablets 5 mg, as the test formulation vs reference formulation, tablets 5 mg) in 23 healthy male volunteers who received a single 5 mg oral dose of each preparation. The study was open, randomized with a two-period crossover design and a 7-day washout period. Plasma samples were obtained over a 48-h interval. The finasteride concentrations were determined by high-pressure liquid chromatography (HPLC) coupled to tandem mass spectrometry (LC-MS-MS). The analytical method developed has a limit of quantitation (LOQ) of 0.50 ng/ml in plasma. For the quality control the measured concentration was 2.05 +/- 0.14 ng/ml (mean +/- SD, n = 30) with a precision of 6.9% and an accuracy of 2.55% at a concentration of the starting solution of 2.00 ng/ml, while with 20.00 ng/ml starting solution the measured concentrations were 20 +/- 0.80 ng/ml (n = 30) with a precision of 3.81% and an accuracy of 0.09%. From the plasma finasteride concentration vs time curves the following pharmacokinetics parameters were obtained: AUC0-48, AUC0-infinity, Cmax, Cmax/AUC0-48, Ke, elimination half-life and tmax. Geometric mean test/reference formulations individual percent ratio was 95.71 for AUC0-48 h and 88.70% for Cmax. The 90% confidence interval for the geometric mean of the individual ratio test/reference formulations was 95.70-120.20% for AUC0-48 h, 94.60-121.30 for AUC0-infinity and 88.70-108% for Cmax. Since for both Cmax or AUC the 90% Cl values are within the interval proposed by the Food and Drug Administration, the test formulation is bioequivalent to the reference formulation for both the rate and extent of absorption after single dose administration.     

Bioequivalence study of two capsule formulations containing diacerein 50 mg in healthy human subjects

This study presents the results of a two-way, two-period, two-treatment crossover investigation in 12 healthy Indian male subjects to assess the bioequivalence of two oral formulations containing 50 mg of diacerein (CAS 13739-02-1). Both formulations were administered orally as a single dose separated by a one-week washout period. The content of diacerein in plasma was determined by a validated HPLC method with UV detection. The formulations were compared using the parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)), peak plasma concentration (Cmax), and time to reach peak plasma concentration (tmax). The results of this study indicated that there were no statistically significant differences between the logarithmically transformed AUC(0-infinity) and Cmax, values of the two preparations. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limit of 0.8-1.25 and the relative bioavailability of the test formulation was 96.63% of that of the reference formulation. Thus, these findings clearly indicate that the two formulations are bioequivalent in terms of rate and extent of drug absorption.     

Bioavailability investigation of two different oral formulations of Tetrazepam

Two different oral tetrazepam (CAS 10379-14-3) formulations (Tetrazepam-ratiopharm film-coated tablets as test preparation and tablets of a reference preparation marketed in France) were investigated in 20 healthy volunteers in order to prove bioequivalence between these preparations. A single 50 mg oral dose was given according to a randomised two-way crossover design in the fasted state. Blood samples for determination of tetrazepam plasma concentrations were collected at pre-defined time points up to 96 h following drug administration. A washout period of 14 days separated both treatment periods. Tetrazepam plasma concentrations were determined by means of a validated LC-MS/MS method. Values of 3873.08 ngh/ml (test preparation) and 3930.69 ngh/ml (reference preparation) for the parameter AUC0-infinity demonstrate an nearly identical extent of drug absorption. Maximum concentrations (Cmax) of 482.08 ng/ml and 465.14 ng/ml were achieved for test and reference preparation. Time to reach maximum plasma concentration (tmax) was 1.39 hours for both preparations. Cmax and AUC0-infinity-values were tested parametrically by an analysis of variance (ANOVA). Bioequivalence was concluded if the 90% confidence intervals of the T/R-ratios were in the range of 80%-125% for AUC0-infinity and 70%-143% for Cmax. Based on the results obtained in this study, bioequivalence between the test and the reference preparation was demonstrated.     

Bioavailability investigation of two different oral formulations of methylprednisolone

Two different oral methylprednisolone (CAS 83-43-2) formulations (Methylprednisolon-ratiopharm 8 mg tables as test preparation (T) and tablets of a reference preparation (R)) were investigated in 16 healthy volunteers in order to prove bioequivalence between these preparations. A single 8 mg oral dose was given according to a randomised two-way crossover design in the fasted state. Blood samples for determination of methylprednisolone plasma concentrations were collected at pre-defined time points up to 16 h following drug administration. A washout period of 3 days separated both treatment periods. Methylprednisolone plasma concentrations were determined by means of a validated HPLC method. Values of 342.53 ng.h/ml (test preparation) and 336.61 ng.h/ml (reference preparation) for the parameter AUC0-infinity demonstrate an nearly identical extent of drug absorption. Maximum concentrations (Cmax) of 66.58 ng/ml and 70.51 ng/ml were achieved for test and reference preparation. Time to reach maximum plasma concentration (tmax) was 2.2 h for both preparations. Cmax and AUC0-infinity-values were tested parametrically by the two one-sided t-test procedure. Bioequivalence was concluded if the 90% confidence intervals of the T/R-ratios were in the range of 80-125% for AUC0-infinity and 70-143% for Cmax. Based on the results obtained in this study, bioequivalence between Methylprednisolone ratiopharm and the reference preparation was demonstrated.     

Bioequivalence study of tramadol by intramuscular administration in healthy volunteers

Tramadol hydrochloride (CAS 36282-47-0) is a centrally acting analgesic agent binding to mu opiate receptors. The bioavailability of a new tramadol hydrochloride injection (Limadol) was compared with a commercially available reference product by intramuscular administration in twelve healthy Chinese male volunteers by a standard two-way cross-over trial. Each volunteer received a single 100 mg injection of tramadol HCl in each phase. The bioavailability was compared using the area under the plasma concentration-time curve from time 0 to 30 h (AUC0-30), the area under the plasma concentration-time curve from time 0 to infinity (AUC0-infinity), peak plasma concentration (Cmax), and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed between the Tmax, Cmax, AUC0-30 and AUC0-infinity of the two preparations. It is concluded that test and reference formulations of tramadol hydrochloride are bioequivalent for both the extent and rate of absorption after a single intramuscular injection.     

Pharmacokinetics and comparative bioavailability of two terbinafine hydrochloride formulations after single-dose administration in Chinese healthy subjects

The bioavailability of a new terbinafine (CAS 91161-71-6) preparation was compared with a commercially available original preparation (reference) of the drug in 19 Chinese healthy male volunteers. The study was performed in an open, randomized, single blind two-sequence, two-period crossover design. Under fasting conditions, each subject received a single oral dose of 250 mg terbinafine as a test or reference formulation with a 7-day washout period between the two preparations. The plasma concentrations of terbinafine were analyzed by a sensitive liquid chromatography-ultraviolet spectrometry method. The pharmacokinetic parameters included AUC(0-t) AUC(0-infinity), C(max), t1/2, and T(max). The values of AUC(0-t) demonstrated nearly identical bioavailability of terbinafine from the examined formulations. The AUC(0.48) of terbinafine was 5982.85 +/- 2449.17 and 6761.63 +/- 3140.33 ng x h/ml for the test and reference formulation, respectively. The maximum plasma concentration (C(max)) of terbinafine was 1656.25 +/- 623.18 ng/ml for the test and 1552.07 +/- 660.35 ng/ml for the reference product, respectively. No statistical differences were observed for C(max) and the area under the plasma concentration time curve for terbinafine. The 90% confidence limits calculated for C(max) and AUC from zero to infinity (AUC(0-infinity)) of terbinafine were within the bioequivalence range (80%-125% for AUC). This study shows that the test formulation is bioequivalent to the reference formulation of terbinafine.     

左旋多巴片在健康人体的生物等效性

目的评价2种左旋多巴片(抗震颤麻痹药)在健康人体内的生物等效性。方法 18名健康男性受试者随机交叉给药,分别单次口服左旋多巴片的试验药物或对照药物250 mg,用高效液相色谱法测定左旋多巴的血药浓度,计算2种药物的药代动力学参数,并评价其生物等效性。结果口服左旋多巴片试验药物及对照药物的主要药代动力学参数:t1/2分别为(1.06±0.31),(1.02±0.40)h;Tmax分别为(0.53±0.39),(0.54±0.37)h;Cmax分别为(1.69±0.66),(1.61±0.68)μg.mL-1;AUC0-t分别为(2.00±0.64),(1.85±0.50)μg.h.mL-1;AUC0-∞分别为(2.10±0.64),(1.95±0.55)μg.h.mL-1。试验药物相对于对照药物的平均相对生物利用度F值:AUC0-t为(110.9±33.1)%,AUC0-∞为(111.1±32.4)%。结论 2种左旋多巴片生物等效。     

Comparative test of the bioavailability and pharmacokinetics of 2 oxazepam preparations using high-pressure liquid chromatography

The relative bioavailability and pharmacokinetic profile of two oxazepam preparations were evaluated in 12 normal volunteers by a newly developed HPLC-method. After oral application of one tablet of the test (Noctazepam) and reference preparation, respectively, no statistically significant differences of the AUC, Cmax Tmax and t1/2 were found. As compared to the reference preparation the relative bioavailability of the test preparation as 110%; both preparations are therefore bioequivalent.     

盐酸特比萘芬片在中国健康受试者体内的生物等效性研究

目的 研究盐酸特比萘芬片在中国健康受试者中的药代动力学,评价国产受试制剂与原研参比制剂的生物等效性.方法 采用空腹/餐后、随机、开放、单剂量、两周期、两序列、双交叉试验设计.空腹试验和餐后试验各入组36例健康受试者,随机分为2组,每周期单次空腹或餐后口服盐酸特比萘芬片受试制剂或参比制剂125 mg.用液相色谱-串联质谱...     

Pharmacokinetics and bioequivalence study of a generic amlodipine tablet formulation in healthy male volunteers

Two different tablets containing amlodipine besylate (CAS 111470-99-6) (Vazkor 10 mg tablet as test preparation and 10 mg tablet of the originator product as reference preparation) were investigated in 18 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence between both treatments after oral single dose administration. The study was performed according to an open-label, randomized, two-period cross-over design with a wash-out phase of 21 days. Blood samples for pharmacokinetic profiling were taken up to 144 h post-dose, and amlodipine plasma concentrations were determined with a validated LC-MS/MS method. Maximum plasma concentrations (Cmax) of 6,183.7 pg/ml (test) and 5,366.7 pg/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC(0-infinity)) of 267,231.0 pg x h/ml (test) and 266,061.7 ng x h/ml (reference) were calculated. The median tmax was 5.6 h (test) and 6.1 h (reference). Plasma elimination half-lives (t 1/2) were 46.46 h (test) and 45.34 h (reference). Both primary target parameters AUC(0-infinity) and Cmax were tested parametrically by analysis of variance (ANOVA); 90% confidence intervals were between 93.20%-107.16% (AUC(0-infinity) and 103.36%-123.13% (Cmax). Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80%-125%.     

The bioequivalence of doxycycline in two preparations in capsule form]

In a randomized cross-over study the bioavailability of doxycycline (CAS 17086-28-1) in two preparations was examined by determining AUC and Cmax. The bioavailability of Doxycyclin-Kapseln (T = test preparation) relatively to a reference preparation (R) in 20 healthy subjects. Statistical analysis of plasma concentration curve and maximum concentration showed no differences between the pharmaceutical preparations tested. Both preparations proved to be bioequivalent.     

盐酸利托君片在中国健康人体的生物等效性

目的评价2种国产盐酸利托君片在中国健康人体的生物等效性。方法22名健康女性受试者随机交叉单剂量口服盐酸利托君片试验药物或对照药物,各10 mg。用高效液相色谱-串联质谱法测定血浆中盐酸利托君浓度;用DAS2.0软件计算药代动力学参数,并对2种药物进行生物等效性评价。结果试验药物和对照药物的主要药代动力学参数:Cmax分别为(5.71±1.83)和(5.61±2.03)ng.mL-1;Tmax分别为(0.54±0.45)和(0.46±0.24)h;t1/2分别为(3.64±3.99)和(4.25±4.02)h;AUC0-t分别为(12.31±5.20)和(12.01±5.42)h.ng.mL-1。AUC0-t、AUC0-∞、Cmax的90%可信区间分别为95.8%～111.6%、92.3%～118.9%和95.4%～108.2%。试验药物相对于对照药物的生物利用度F为(105.3±19.96)%。结论试验药物和对照药物生物等效。     

Bioavailability investigation of two different oral formulations of doxepin

Two different oral doxepin (CAS 1668-195) formulations (Doxepin-ratiopharm 25 mg film-coated tablets as test preparation and 25 mg dragées of the reference preparation) were investigated in 30 healthy male and female volunteers in order to prove bioequivalence between these preparations. A single 75 mg oral dose (3 units of test or reference preparation) was given according to a randomised two-way cross-over design in the fasted state. Blood samples for determination of plasma concentration of doxepin and its metabolite N-desmethyldoxepin were collected at pre-defined time points up to 168 h following drug administration. A wash-out period of three weeks separated both treatment periods. Doxepin and N-desmethyldoxepin plasma concentrations were determined by means of a validated LC-MS/MS method. Values of 193,463 pgh/ml (test preparation) and 197,988 pg h/ml (reference preparation) for doxepin as well as values of 313,298 pg h/ml (test preparation) and 306,663 pgh/ml (reference preparation) for N-desmethyldoxepin for the parameter AUC0-infinity demonstrate a nearly identical extent of drug absorption. Maximum concentrations (Cmax) for doxepin/N-desmethyldoxepin of 15,960.06/6,883.69 pg/ml and 18,614.73/6,846.62 pg/ml were achieved for test and reference preparation. Time to reach doxepin maximum plasma concentration (tmax) was 1.98 h for both preparations and for N-desmethyldoxepin tmax was 4.52 h (test preparation) and 4.15 h (reference preparation). Cmax and AUC0-infinity values were tested for statistically significant differences by means of the Two One-Sided T-Tests procedure following ln-transformation of data. Bioequivalence was assumed if the 90% confidence intervals of the T/R-ratios were in the range of 80%-125% for ln-transformed AUC0-infinity and 70%-143% for ln-transformed Cmax. Based on the results obtained in this study, bioequivalence between the test and the reference preparation was demonstrated.