Indian Male Subjects Research Articles

Application of a UPLC-MS/MS method for the analysis of alosetron in human plasma to support a bioequivalence study in healthy males and females.

A simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of alosetron (ALO) in human plasma. The assay method involved solid-phase extraction of ALO and ALO 13C-d3 as internal standard (IS) on a LichroSep DVB-HL (30 mg, 1 cm(3) ) cartridge. The chromatography was performed on an Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 µm) column using acetonitrile and 2.0 mm ammonium formate, pH 3.0 adjusted with 0.1% formic acid (80:20, v/v) as the mobile phase in an isocratic mode. For quantitative analysis, the multiple reaction monitoring transitions studied were m/z 295.1/201.0 for ALO and m/z 299.1/205.1 for IS in the positive ionization mode. The method was validated over a concentration range of 0.01-10.0 ng/mL for ALO. Post-column infusion experiment showed no positive or negative peaks in the elution range of the analyte and IS after injection of extracted blank plasma. The extent of ion-suppression/enhancement, expressed as IS-normalized matrix factor, varied from 0.96 to 1.04. The assay recovery was within 97-103% for ALO and IS. The method was successfully applied to support a bioequivalence study of 1.0 mg alosetron tablets in 28 healthy Indian male and female subjects.

Bioequivalence Study of Nicotine 4 Mg Lozenges in Indian Healthy Adult Human Male Smoker Subjects

Nicotine Lozenges are used to aid smokers wishing to quit or reduce prior to quitting. The aim of this study was to determine the bioequivalence of a test and reference formulation of Nicotine 4 mg Lozenge. This single dose, randomized, 2-period, 2‑sequence, laboratory-blinded, crossover design study was conducted in 28 Indian healthy adult human male smoker subjects under fasting conditions with a washout period of 7 days. Study formulations were administered after a 10 hrs overnight fast. Blood samples for pharmacokinetic profiling were taken postdose up to 16 hrs. Safety was evaluated through the assessment of adverse events, and laboratory tests. Plasma concentrations of Nicotine were determined with a validated LC-MS/MS method. Bioequivalence between the products was determined by calculating 90% confidence interval (90% CI) for the ratio of Cmax and AUC0-t values for the test and reference products, using logarithmic transformed data. The 90% CI of Nicotine were 109.85-123.32 and 101.48-115.41 for Cmax and AUC0-t respectively. Since the 90% CI for Cmax and AUC0-t were within the 80-125% interval, it was concluded that the two formulations of Nicotine 4 mg Lozenge are bioequivalent in their rate and extent of absorption.

A Bioequivalence Study of Nicotine 2 Mg Lozenges in Indian Healthy Adult Human Male Smoker Subjects

Nicotine Lozenges are used to aid smokers wishing to quit or reduce prior to quitting. The aim of this study was to determine the bioequivalence of a test and reference formulation of Nicotine 2 mg Lozenge. This single dose, randomized, 2-period, 2‑sequence, laboratory-blinded, crossover design study was conducted in 28 healthy adult Indian male subjects under fasting conditions with a washout period of 7 days. Study formulations were administered after a 10-hour overnight fast. Blood samples for pharmacokinetic profiling were taken post-dose up to 16 hours. Safety was evaluated through the assessment of adverse events, and laboratory tests. Plasma concentration of Nicotine was determined with a validated LC-MS/MS method. Bioequivalence between the products was determined by calculating 90% confidence intervals (90% CI) for the ratio of AUC0-t and Cmax values for the test and reference products, using logarithmic transformed data. The 90% confidence intervals of Nicotine were 96.16-119.10 and 92.16-111.51 respectively. Since the 90% confidence intervals for Cmax and AUC0-t were within the 80 – 125% interval, it was concluded that the two formulations of Nicotine 2 mg Lozenge are bioequivalent in their rate and extent of absorption.

Sensitive, selective and rapid determination of lafutidine in human plasma by solid phase extraction-liquid chromatography-tandem mass spectrometry

A simple, sensitive and high throughput liquid chromatography-tandem mass spectrometry method has been developed for the determination of lafutidine in human plasma. Sample clean-up involved solid phase extraction of lafutidine along with ranitidine as the internal standard from 100 μL of human plasma. The chromatographic separation is achieved within 2.5 min on a Grace Denali C18 (50 × 4.6 mm, 5 μ) column using 2 mM ammonium acetate, pH 3.0 adjusted with acetic acid and acetonitrile (20: 80, v/v) as the mobile phase. The precursor → product ion transitions for lafutidine (m/z 432.2 → 351.4) and IS (m/z 315.3 → 176.3) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring and positive ion mode. The method is validated over a wide dynamic concentration range of 0.25–1000 ng/mL. The mean relative recovery for lafutidine across quality controls is 97.9%. The relative matrix effect between eight different plasma lots, expressed as coefficient of variation of the slopes of the calibration lines is 1.94. The method is applied to a bioequivalence study of 10 mg lafutidine tablet formulation in 26 healthy Indian male subjects under fasting condition. The reproducibility of study data is demonstrated by analysis of 93 incurred samples.

The diagnosis of osteoporosis among South Indian male and female subjects with low impact hip fracture and comparison between Indian Council of Medical Research and Caucasian Bone Mineral Density Databases

The diagnosis of osteoporosis among South Indian male and female subjects with low impact hip fracture and comparison between Indian Council of Medical Research and Caucasian Bone Mineral Density Databases

Cardio-respiratory response of young adult Indian male subjects to stress: Effects of progressive muscle relaxation

<b>Background:</b> Stress and anxiety have become an integral part of our lives. Of late, this has resulted in the increase in incidence of hypertension and coronary heart disease. <b>Objectives:</b> To assess the effect of progressive muscle relaxation (PMR) on young adult males and its role in the modulation of cardio-respiratory response on exposure to stress. <b>Materials and Methods:</b> This prospective cross-sectional study was conducted in a tertiary care referral hospital. Undergraduate male students under stress were chosen for the study. Fasting blood samples were drawn to analyze sugar and lipid profile, followed by anthropometric measurements and ECG. In the resting condition, blood pressure, pulse rate, and spirometric parameters; forced vital capacities (FVC), and forced expiratory volume in 1 sec (FEV ₁ %) were measured. Then, they were made to exercise with bicycle ergometer and post exercise, the vital parameters were recorded. All subjects were given a training of Jacobson's Progressive Muscular Relaxation and asked to practice this technique for 3 months. All parameters were re-evaluated. <b>Results:</b> Significant decreases in resting heart rate, systolic blood pressure and diastolic blood pressure, total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol levels of subjects were seen after PMR training. Exercise-induced rise in heart rate and blood pressure were also significantly less in subjects following PMR training. <b>Conclusion:</b> Progressive muscle relaxation helps in modulation of heart rate, blood pressure, and lipid profile in healthy normal adult male individuals.

Bioanalysis of tolvaptan, a novel AVP‐V2 receptor antagonist in human plasma by a novel LC‐ESI‐MS/MS method: a pharmacokinetic application in healthy South Indian male subjects

A simple, rapid and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) assay method is proposed for the determination of tolvaptan in human plasma samples using tolvaptan d7 as internal standard (IS). Analyte and the IS were extracted from 100 μL of human plasma via simple liquid-liquid extraction. The chromatographic separation was achieved on a C18 column using a mixture of methanol and 0.1% formic acid buffer (80:20, v/v) as the mobile phase at a flow rate of 1.0 mL/min. The calibration curve obtained was linear (r(2) ≥ 0.99) over the concentration range of 0.05-501 ng/mL. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The intra-day and inter-day precision (coefficient of variation) and accuracy results in three validation batches across five concentration levels were well within the acceptance limits. A run time of 2.0 min for each sample made it possible to analyze more samples in a short time, thus increasing the productivity. The proposed method was successfully applied to a pharmacokinetic study of 15 mg and 60 mg tolvaptan tablet formulation in healthy South Indian male subjects under fasting condition.

Liquid chromatography–tandem mass spectrometric assay for aliskiren, a novel renin inhibitor in micro‐volumes of human plasma: a pharmacokinetic application in healthy South Indian male subjects

This paper describes a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry assay for the determination of aliskiren in human plasma using nevirapine as an internal standard. Analyte and the internal standard were extracted from 100 μL of human plasma via liquid-liquid extraction using tert-butyl methyl ether. The chromatographic separation was achieved on a C18 column using a mixture of acetonitrile and 0.1% formic acid (90:10, v/v) as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear (r(2) ≥ 0.99) over the concentration range of 0.10-1013 ng/mL. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. A run time of 2.2 min for each sample made it possible to analyze a greater number of samples in a short time, thus increasing the productivity. The proposed method was found to be applicable to clinical studies.

Application of a Reliable LC-MS/MS Method for Determination of Rizatriptan in Healthy Subject Samples: Demonstration of Assay Reproducibility by Incurred Sample Reanalysis

A reliable, rapid, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of rizatriptan in human plasma using sumatriptan as internal standard (IS). The analyte and IS were extracted from 300 μL human plasma via liquid-liquid extraction and the chromatography was achieved on Hypurity C18 (50 mm × 4.6 mm, 5 μm) column under isocratic conditions. Detection of rizatriptan and IS was done by tandem mass spectrometry, operating in positive ionization and multiple-reaction monitoring mode. The limit of detection and lower limit of quantitation of the method were 0.04 and 0.20 ng/mL, respectively, with a linear dynamic range of 0.20–60.0 ng/mL. The intrabatch and interbatch precision (% CV) was ≤8.4% while the mean extraction recovery was &gt;78% across quality control levels. Bench top stability, freeze and thaw stability, processed sample stability, and long-term stability in plasma were evaluated at two quality control levels. It was successfully applied to a bioequivalence study of 10 mg rizatriptan orally disintegrating tablet formulation in 40 and 32 healthy Indian male subjects under fasting and fed conditions, respectively. The reproducibility in the measurement of study data was demonstrated by reanalysis of 254 incurred samples.

Sensitive and Selective Determination of Diflunisal in Human Plasma by LC-MS

A reliable and sensitive liquid chromatography-tandem mass spectrometry assay has been proposed for the selective determination of diflunisal in the presence of its glucuronide metabolites. The analyte and clofibric acid as internal standard (IS) are extracted from 50 µL of human plasma by solid-phase extraction. Chromatographic separation is conducted on a Prodigy ODS 3V column (150 × 4.6 mm, 5 µm) under isocratic conditions. The possible interference of acyl glucuronide and phenolic glucuronide, the two major inactive metabolites of diflunisal, is also checked in plasma samples. Detection of the analyte and IS is achieved by tandem mass spectrometry, operating in negative ionization and multiple reaction monitoring acquisition mode. The limits of detection and quantitation of the method are 0.10 and 1.00 µg/mL, respectively, with a linear dynamic range of 1.00-160 µg/mL for diflunisal. The intra-batch and inter-batch precision (percent coefficient of variation) is ≤4.2% and the mean recovery is >92% for diflunisal across quality control levels. The method is successfully applied to a bioequivalence study of a 500 mg diflunisal tablet formulation in 30 healthy Indian male subjects under fasting conditions. The reproducibility in the measurement of study data is demonstrated by the reanalysis of 120 incurred samples.

A SIMPLE HPLC-UV METHOD DEVELOPMENT AND VALIDATION FOR THE QUANTIFICATION OF DEXIBUPROFEN APPLIED IN BIOEQUIVALENCE STUDY

A simple, rapid, and sensitive HPLC with UV detection was developed and validated for the determination of dexibuprofen in human plasma. The method involves extracting dexibuprofen with acetonitrile. Chromatographic separation was carried out on a C18 column using mixture of acetonitrile:methanol:potassium dihydrogen phosphate as mobile phase with UV detection at 222 nm. The retention time of dexibuprofen was 4.720 ± 0.3 min. The method was validated for selectivity, linearity, and range; intra-day and inter-day accuracy; and precision and stability. The developed and validated method was applied to a single oral dose of 400 mg dexibuprofen reference formulations (IBUSOFT 400 tablets manufactured by Emcure Pharmaceuticals Ltd, Pune, India) or test formulations (Medley Pharmaceuticals Ltd, Mumbai, India) that were administered to Indian healthy human male subjects. Serial blood samples were collected for 12 hr after administration of formulations. Pharmacokinetic parameters were determined for both the formulations. Cmax, AUC0-t and AUC0-inf, were evaluated for bioequivalence after log-transformation of data using ANOVA with a 90% confidence interval level. All of the tested parameters were within the acceptable range of 80–125%. The present method is simple and readily applicable to pharmacokinetic and routine bioequivalence studies of these compounds with an acceptable sensitivity.

Development of an SPE-LC–MS/MS method for simultaneous quantification of bosentan and its active metabolite hydroxybosentan in human plasma to support a bioequivalence study

A highly sensitive, selective and rapid bioanalytical method has been developed for the simultaneous determination of bosentan and hydroxybosentan in human plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analytes and their deuterated analogs were quantitatively extracted from 100 μL human plasma by solid phase extraction. The chromatographic separation of analytes was achieved on a Thermo Hypurity C18 (100 mm × 4.6 mm, 5 μ) analytical column with a resolution factor of 2.4 under isocratic conditions. The method was validated over a dynamic concentration range of 0.4-1600 ng/mL for bosentan and 0.2-250 ng/mL for hydroxybosentan. Ion-suppression effects were investigated by post-column infusion of analytes. The precision (%CV) values for the calculated slopes of calibration curves, which would reflect the relative matrix effect, were less than 1.2% for both the analytes. The intra-batch and inter-batch precision (%CV) across quality control levels was ≤4.0% and the mean relative recovery was >94% for both the analytes. The method was successfully applied to a bioequivalence study of 125 mg tablet formulation (test and reference) in 12 healthy Indian male subjects under fasting condition. The ratios of mean log-transformed values of C(max), AUC(0-t) and AUC(0-inf) and their 90% CIs varied from 91.3 to 104.7%. The percentage change for incurred sample reanalysis (ISR) was within ±13.0%.

Bioequivalence study of two Losartan tablet formulations with special emphasis on cardiac safety

To study the bioequivalence of Losartan Potassium Tablets 50 mg manufactured by Micro Labs Ltd. India to Cozaar® Tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in normal healthy adult subjects under fasting condition along with the comparative safety evaluation of both treatments. The in vitro dissolution studies were carried out on 12 units each of test and reference products using the paddle method and dissolution media like water, 0.1 N hydrochloric acid with pH 1.2, pH 4.5 acetate buffer and pH 6.8 phosphate buffer. An open label, randomized, two-treatment, two-period, two-sequence, crossover bioequivalence study with a washout period of 7 days was conducted in 60 healthy Indian male subjects. Serial blood samples were collected after drug administration in each study period. Plasma concentrations of losartan and losartan acid were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of losartan and losartan acid were determined using a non compartmental model. Occurrence of adverse events, change in systolic blood pressure, diastolic blood pressure, heart rate and QT interval from the baseline to 3.50 h post dose were studied and compared between the two treatments as safety parameters. The in vitro study proved the essential similarity of both the formulations as evident from the similarity factor of > 50% in all the dissolution media. The ratios for geometric least square means and 90% confidence intervals were within the acceptance criteria of 80% to 125% for log transformed C(max), AUC(0-t) and AUC(0-∞) for losartan. No statistically significant difference between the two treatments was observed for either of the safety parameters. The test product Losartan Potassium tablets 50 mg manufactured by Micro Labs Limited, India was bioequivalent to Cozaar® tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in terms of rate and extent of absorption. Both treatments were well tolerated and had similar non significant effect on the safety parameters.

Association of Resistin with Metabolic Syndrome in Indian Subjects

The role of resistin in insulin sensitivity and metabolic syndrome has been controversial until now. Increased plasma/serum resistin levels are associated with metabolic syndrome and insulin resistance. The aim of this study was to investigate the relationship between serum resistin levels with markers of metabolic syndrome in males. A total of 386 male volunteers were enrolled in a case-control study. All of the enrolled volunteers were analyzed to confirm metabolic syndrome following the guidelines of National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) of 2001. Of the 386 volunteers, 192 were categorized as cases of metabolic syndrome, whereas 194 were registered as controls without metabolic syndrome. Volunteers enrolled in the study were analyzed for anthropometrical parameters, lipid profile status, insulin, insulin resistance, and resistin. Higher levels of resistin were observed in cases when compared to controls (12.49 ± 4.73 ng/mL vs. 6.99 ± 1.98 ng/mL). Resistin was positively and significantly associated with serum triglyceride, cholesterol, and very-low-density lipoprotein, whereas it was negatively and significantly associated with serum high-density lipoprotein (HDL) levels. Multiple regression analysis of the data observed indicated that the triglyceride level was the major determinant for the development of metabolic syndrome in male samples. This study demonstrates a positive correlation between resistin and factors of metabolic syndrome, except for HDL cholesterol (HDL-C), which was found to be negatively correlated in Indian male subjects. The study also found resistin to be a suitable peripheral blood marker.

Application of a rapid and sensitive liquid chromatography–tandem mass spectrometry method for determination of bumetanide in human plasma for a bioequivalence study

A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of bumetanide in human plasma using tamsulosin as internal standard (IS). The analyte and IS were extracted from 200 μL of human plasma via solid phase extraction and the chromatographic separation was achieved on Peerless Basic C18 (100 mm × 4.6 mm, 3 μm) column under isocratic conditions. Detection of bumetanide and IS was done by tandem mass spectrometry, operating in positive ionization and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for bumetanide and IS were m/z 365.2→240.2 and 409.2→228.2 respectively. The method was fully validated as per the US FDA guidelines. The limit of detection and lower limit of quantitation of the method were 0.03 and 0.30 ng/mL respectively with a linear dynamic range of 0.30-200.0 ng/mL for bumetanide. The intra-batch and inter-batch precision (% CV) was ≤6.9% while the mean extraction recovery was >90% across quality control levels. The method is selective in presence of four diuretic drugs and some commonly used medications by healthy volunteers. It was successfully applied to a bioequivalence study of 2mg bumetanide tablet formulation in 10 healthy Indian male subjects under fasting condition. The reproducibility in the measurement of study data was demonstrated by reanalysis of 42 incurred samples.

Anthropometric measurements to design best-fit femoral stem for the Indian population.

Background:The standard commercially available marketed prostheses sometimes may not be the best fit to Indian patients because of the large anatomic variation. Orthopedic surgeons always stress the need for a proper implant–patient match in hip joint replacements, in particular, for a cementless femoral stem. The complications of mismatch are aseptic loosening, improper load distribution, and discomfort. The present study was undertaken to compare the differences in dimensions between femurs of elderly Indians and those of populations from other regions in order to solve the problem of a possible geometric mismatch between a selected implant and the hip joint as far as Indian patients are concerned.Materials and Methods:Measurements were made using computer aided design techniques on computed tomography (CT) scanned images of 98 femurs (56 left and 42 right). The software used to convert the CT images into solid models was MIMICS® (Materialize, Inc., Leuven, Belgium). The geometrical parameters, viz., the femoral head offset, femoral head center (HC), femoral head diameter, femoral head relative position, position of shaft isthmus, neck-shaft angle, bow angle, femoral neck length, canal flare index, femoral length, and canal width at various locations, were chosen to design best-fit standard femoral stems for cementless insertion. These data were compared with the published data of other countries.Results:A difference of 16.8% was found in the femoral head offset between Indian and Swiss populations, which can affect soft tissue tension and range of motion. At a distance of 20 mm above the lesser trochanter (LT), the anteroposterior (AP) canal width was found to differ by 45.4%, when compared with a French population which can affect the mechanical stability of femoral stem. Femoral dimensions of Indian male and female subjects have also been compared and differences evaluated. At the LT, the aspect ratio (ratio of mediolateral canal width and AP canal width) in case of males (1.198) is approximately13% higher than that of females (1.059).Conclusions:This study indicates a need for redesign of femoral stems. The obtained anthropometric femoral dimensions can be used to design and develop indigenous hip joint prosthesis in India. The results of this study can also be used in forensic anthropometric studies.

Pharmacokinetic Profiling and Bioequivalence Assessment of Two Marketed Brands of Nevirapine Tablets in Healthy Indian Volunteers

Nevirapine (CAS 129618-40-2), a non-nucleoside reverse transcriptase inhibitor, has been effectively used for treatment of HIV-infected patients. A randomized, two-way, crossover study was conducted in 24 fasting, healthy, Indian male subjects to compare plasma pharmacokinetic profile and single-dose tolerability of a new nevirapine tablet formulation (test, T) with that of a reference (R) tablet. Each volunteer received T and R formulations separated by at least 19 days of drug free wash-out period. Plasma concentrations of nevirapine, determined up to 288 h post dose by a sensitive and validated HPLC assay, were utilized to assess pharmacokinetic parameters such as the maximum observed plasma concentration (Cmax), time to Cmax (tmax), and area under plasma concentration curve (AUCinfinity). The primary plasma pharmacokinetic parameters of anti-retroviral substances, Cmax and AUCinfinity, were comparable for either of the formulations. Oral absorption of nevirapine was almost complete within 5 h. Geometric mean ratios (% reference) of AUCinfinity and Cmax and their 90% confidence intervals were 96.9 [93.69-100.24] and 100.8 [94.61-107.4], respectively. As the 90% confidence intervals of the geometric mean ratio were entirely within 80 to 125% for log-transformed parameters, the two formulations were considered bioequivalent in the extent and rate of absorption. Both formulations exhibited similar tolerability under fasting conditions.

Bioequivalence Study of Two Formulations Containing 400 mg Dexibuprofen in Healthy Indian Subjects

This study presents the results of two-period, two-treatment crossover investigations on 24 healthy Indian male subjects to assess the bioequivalence of two oral formulations containing 400 mg of dexibuprofen (CAS 51146-56-6). An attempt was also made to study the pharmacokinetics of dexibuprofen in the local population of Indian origin. Both of the formulations were administered orally as a single dose separated by a one-week washout period. The concentration of dexibuprofen in plasma was determined by a validated HPLC method with UV detection using carbamazepine as internal standard. 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 (C(max)), and time to reach peak plasma concentration (t(max)). The results of this investigation indicated that there were no statistically significant differences between the logarithmically transformed AUC(0-infinity), and C(max) values of the two preparations. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and C(max) were within the bioequivalence limit of 0.8-1.25 and the relative bioavailability of the test formulation was 99.04% of that of reference formulation. Thus, these findings clearly indicate that the two formulations are bioequivalent in terms of rate and extent of drug absorption. Both preparations were well tolerated with no adverse reactions observed throughout the study.

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.

Bioequivalence study of two tablet formulations containing rimonabant 20 mg in healthy Indian subjects

A randomized, two-treatment and two-way crossover study on twelve healthy Indian male subjects was conducted to assess the bioequivalence of two tablet formulations containing 20 mg of rimonabant (CAS 158681-13-1). Both of the formulations were administered orally as a single dose with a 45-day washout period between two dosing sessions. The content of rimonabant 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 investigation 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 96.62% 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.