Comparative bioavailability of two cefadroxil products using serum and urine data in healthy human volunteers

1. The aim of the present study was to assess the bioequivalence of two cefadroxil products, namely Ultracef (a reference product) in the form of a 500 mg capsule (produced by Bristol-Myers Squibb Laboratories, Princeton, NJ, USA) and Roxil (a test product) in the form of a 500 mg capsule (produced by Tabuk Pharmaceutical Manufacturing, Tabuk, Saudi Arabia). 2. The study was performed under US Food and Drug Administration (FDA) guidelines (http://www.fda.gov/cder) on 24 healthy male subjects. Both products were administered orally as a single dose (1 x 500 mg capsule) separated by a 1 week washout period. Following oral administration, blood and urine samples were obtained and analysed for cefadroxil concentrations using a sensitive and specific HPLC assay. 3. There were no statistically significant differences between the two products in either the mean concentration-time profiles or the cumulative urinary excretion of cefadroxil at various times. Similarly, no statistical significance was observed in the pharmacokinetic parameters reflecting rate and extent of drug absorption. The relative extent of drug absorption, assessed by calculating the area under the curve (AUC) ratio for Roxil/Ultracef for 10 h and for infinity was 0.94 with 90% confidence limits (CL) of 0.91-0.98. In agreement with serum data, the average ratio (Roxil/Ultracef) of the cumulative amount of cefadroxil excreted in urine 10 h after the dose was found to be 0.97, with 90% CL of 0.88-1.05. The CL of the AUC and cumulative urinary excretion ratios are within the FDA accepted limits for bioequivalent products (0.80-1.25). 4. These findings show that serum and urine data of cefadroxil are in agreement and indicate that Roxil (the test product) and Ultracef (the reference product) are bioequivalent in terms of the rate and extent of drug absorption.     

Comparative bioavailability of two ramipril formulations after single-dose administration in healthy volunteers

OBJECTIVE: To assess the bioequivalence of a ramipril 5 mg tablet formulation (ramipril test formulation from Laboratórios Biosintética Ltda (Sao Paulo, Brazil) and Triatec from Aventis Pharma (Sueano, Brazil) standard reference formulation) in 26 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, 2-period crossover design with a 2-week washout interval. Plasma samples were obtained over a 36-hour period. Plasma ramipril and ramiprilat concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the ramipril and ramiprilat plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUClast, AUCinf and Cmax. RESULTS: The limit of quantification was 0.2 ng x ml(-1) and 1.0 ng x ml(-1) for ramipril and ramiprilat, respectively. The geometric means and 90% confidence intervals (CI) for Ramipril/Triatec and Ramiprilat/Triatec percent ratios were: 104.69% (90% CI = 93.21-117.59%) for Cmax, 102.49% (90% CI = 92.76-113.24%) for AUClast, 103.60% (90% CI = 93.56 114.73%) for AUCinf, 108.48% (90% CI = 98.86-119.03%) for Cmax, 105.88% (90% CI = 101.55-110.39%) for AUClast, 97.30% (90% CI = 90.17-104.99%) for AUCinf, respectively. CONCLUSION: Since the 90% CI for AUClast, AUCinf and Cmax ratios were within the 80-125% interval proposed by the U.S. FDA, it was concluded that the ramipril formulation produced by Laboratórios Biosintética Ltda is bioequivalent to the Triatec formulation in both rate and extent of absorption.     

Comparative bioavailability of two capsule formulations of ofloxacin in healthy volunteers after a single dose administration

Abstract

The bioavailability of two ofloxacin (OFX) tablet formulations (OTT, test formulation from Laboratorio Atral SA - Portugal, and Tarivid, reference formulation from Hoechst AG - Germany) were compared in 24 (12M, 12F) healthy volunteers who received a single oral dose of 200 mg of each formulation in an open, randomized, two-period crossover fashion with a 14 day washout interval between doses. Plasma samples were obtained over a 24 h interval and OFX concentrations were determined by HPLC with UV detection. From the OFX plasma concentration vs time curves, the AUC_[0-24] (area under the concentration vs time curves from 0 to 24 h), AUC_[0-α] (area under the concentration vs time curves extrapolated to infinity), C_max (maximum concentration achieved), t_max (time to achieve C_max), t_1/2 (terminal first order elimination half-life), and elimination constant (K_e) were obtained. All these variables were analyzed using both parametric and non-parametric statistics. The two OFX tablet brands did not show statistically significant differences in bioavailability as assessed by the statistical analysis of AUC_[0-24] (14.8 and 14.7μg h ml^?1, respectively for OTT and Tarivid), AUC_[0-α] (16.0 and 15.6 μg h ml^?1), C_max (2.9 and 3.1 μg/ml), t_max (0.8 and 1.5 h), t_1/2 (5.9 and 5.6 h), and K_e (0.12 and 0.13 h^?1) values. Based on these results and on the United States Food and Drug Administration (FDA) requirements [1993], both formulations were considered to be bioequivalent.     

Comparative bioavailability of two sertraline tablet formulations after single-dose administration in healthy Thai volunteers

OBJECTIVE: To compare the bioavailability of two sertraline tablet (50 mg) formulations (Serlift from Ranbaxy Laboratories Ltd., Gurgaon Haryana, India, as a test formulation and Zoloft from Pfizer Australia Pty Ltd., West Ryde, New South Wales, Australia, as a reference formulation) in 24 healthy Thai male volunteers under fasting condition. MATERIALS AND METHODS: A randomized, 2-treatment, 2-period, 2-sequence, single-dose, crossover study with a washout period of 3 weeks, was conducted in 24 healthy Thai male volunteers. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours following drug administration. Plasma concentrations of sertraline were determined using validated LC-MS/MS method. Noncompartmental pharmacokinetics and statistical analyses were performed using SAS software for Windows, release 9.1 (SAS Institute Inc., Cary, NC, USA). RESULTS: The ratio of least square means and the 90% confidence intervals (CI) of the log-transformed data were 0.9950 (0.9111-1.0866) for Cmax, 1.0153 (0.9576-1.0764) for AUC(0-t) and 1.0110 (0.9510-1.0747) for AUC(0-infinity). In addition, the median tmax values for the test and reference formulations were similar (5.00 h). The 90% CI for Cmax, AUC(0-t) and AUC(0-infinity) were within the 0.8-1.25 interval of the US-FDA. CONCLUSIONS: The test formulation (Serlift, Ranbaxy Laboratories Ltd., Gurgaon, Haryana, India) is bioequivalent to the reference formulation (Zoloft, Pfizer Australia Pty Ltd., West Ryde, New South Wales, Australia) both in terms of rate and extent of absorption after single-dose administration under fasting condition.     

Comparative bioavailability of two losartan formulations in healthy human volunteers after a single dose administration

OBJECTIVE: To compare the bioavailability of two potassic losartan immediate release tablet (50 mg) formulations (Losartan from Laboratórios Cristália Ltd., Brazil, as a test formulation and Cozaar from Merck Sharp & Dohme Farmacêutica Ltd., Brazil, as a reference formulation) in 25 volunteers of both sexes. MATERIAL AND METHODS: The study was conducted in an open, randomized, 2-period crossover design and a 1-week washout period. Plasma samples were obtained over a 24-hour interval. The concentrations of losartan and its active metabolite losartan acid were analyzed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using a selected ion monitoring method. From the losartan and losartan acid plasma concentrations vs. time curves the following pharmacokinetic parameters were obtained: AUClast, AUC0-inf and Cmax. RESULTS: The geometric mean and respective 90% confidence interval (CI) of Losartan/Cozaar losartan percent ratios were 92.9% (82.2-105.0%) for Cmax, 99.0% (92.5-105.9%) for AUClast, and 99.1% (92.7-105.8%) for AUC0-inf. Furthermore, the geometric mean and respective 90% CI of Losartan/Cozaar losartan acid percent ratios were 98.5% (91.5-106.0%) for Cmax, 97.9% (93.3 102.7%) for AUClast, and 98.1% (93.6-102.9%) for AUC0-inf. CONCLUSION: Since the 90% CI for Cmax, AUClast and AUC0-inf were within the 80-125% interval proposed by the US Food and Drug Administration, it was concluded that the potassic losartan immediate release 50 mg tablet was bioequivalent to the Cozaar immediate release 50 mg tablet, according to both the rate and extent of absorption. While there were no significant differences in the bioequivalence assessed by either losartan or losartan acid, future bioequivalence studies on losartan may be performed by quantifying losartan alone as the parent compounds are more discriminative.     

Comparative bioavailability of 4 amoxicillin formulations in healthy human volunteers after a single dose administration

OBJECTIVE: To compare the bioavailability of two amoxicillin oral suspension (250 mg/5 ml) formulations and two amoxicillin capsule (500 mg) formulations (Amoxicilina from Medley S/A Indústria Farmace?tica, Brazil, as test formulations and Amoxil from SmithKline Beecham Laboratórios Ltda., Brazil, as reference formulations) in 48 volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with a randomized two-period crossover design and a one-week washout period. Plasma samples were obtained over a 12-hour interval. Amoxicillin concentrations were analyzed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using the selected ion monitoring method. From the amoxicillin plasma concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-infinity) and Cmax. RESULTS: Geometric mean of Amoxicilina/Amoxil 250 mg/5 ml individual percent ratio was 103.70% for AUC(last), 103.15% for AUC(0-infinity) and 106.79% for Cmax. The 90% confidence intervals were 97.82-109.94%, 97.40 to 109.24%, and 96.38-118.33%, respectively. Geometric mean of Amoxicilina/Amoxil 500 mg capsule individual percent ratio was 93.26% for AUC(last), 93.27% for AUC(0-infinity) and 90.74% for Cmax. The 90% confidence intervals were 85.0-102.33%, 85.12-102.31%, and 80.14-102.73%, respectively. CONCLUSION: Since the 90% CI for both Cmax, AUC(last) and AUC(0-inifnity) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that Amoxicilina 250 mg/5 ml oral suspension and Amoxicilina 500 mg capsule were bioequivalent to Amoxil 250 mg/5 ml oral suspension and to Amoxil capsule 500 mg, respectively, with regard to both the rate and extent of absorption.     

两种国产右旋布洛芬制剂的生物利用度

目的比较两种国产右旋布洛芬制剂的人体生物利用度。方法20名男性健康受试者采用随机分组自身交叉对照给药方案。单剂量口服参比制剂右旋布洛芬片剂及试验制剂右旋布洛芬胶囊各300mg,用HPLC-UV法测定右旋布洛芬血药浓度。用3P97计算机程序求算药动学参数。结果右旋布洛芬试验制剂与参比制剂的主要药动学参数T1/2(2.0±0.7)h,(1.9±0.4)h,T     

头孢羟氨苄咀嚼片的人体生物等效性

目的：评价头孢羟氨苄咀嚼片与参比片剂在人体内生物等效性。方法：采用随机交叉试验设计，20名健康男性受试者分别口服单剂量受试制剂与参比制剂500mg，HPLC法测定血浆中头孢羟氨苄的浓度，用DAS1．0统计软件计算药动学参数并进行生物等效性评价。结果：受试制剂与参比制剂的已。分别为（19．2±2．3）mg·L^-1和（18．4±2．7）mg·L^-1,tmax分别为（0．95±0．22）h和（1．3±0．4）h，t1/2分别为（1．78±0．14）h和（1．73±0．09）h，AUC（0→10）分别为（53．3±7．5）mg·h·L^-1和（54．0±7．4）mg·h·L^-1,AUC（0→∞）分别为（54．4±7．9）mg·h·L^-1和（55．1±7．7）mg·h·L^-1。受试制剂相对于参比制剂的生物利用度为（99．0±7．0）％。结论：两制剂具有生物等效性。     

Comparative bioavailability of two cefdinir suspension formulations in Middle Eastern healthy volunteers after single oral administration

The aim of this study was to compare the bioavailability, after oral administration, of the generic "Adcef Suspension" (test) (125 mg/5 ml cefdinir; CAS 91832-40-5), with that of a commercially available original preparation (reference) (125 mg/ 5 ml cefdinir). For this purpose a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers. The Middle Eastern selected volunteers were divided into two groups of 12 subjects. One group was treated with the reference standard and the other one with the test, with a crossover after the drug washout period of 7 days. Blood samples were collected at fixed time intervals and cefdinir concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC(0-24), AUC(0-infinity), C(max), T(max), K(e) and T1/2 were determined for both formulations and were compared statistically to evaluate the bioequivalence betwee the two brands of cefdinir, using the statistical model recommended by the 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 the statistical evaluation it was concluded that the two formulations exhibit.     

Comparative bioavailability of two different diclofenac formulations in healthy volunteers

The aim of the study was to assess the bioequivalence of two different diclofenac (CAS 15307-86-5) formulations (diclofenac free acid suspension as test formulation and diclofenac resinate suspension, Cataflam, as reference formulation) in 24 healthy volunteers. After an overnight fast, the volunteers received a single oral dose (50 mg) of each formulation, following an open, randomized, two-period crossover design, with a fourteen-day washout interval between doses. Serum samples were obtained over a 24-h interval post-dosing, and were analysed for their diclofenac content by HPLC-UV. No adverse effect was reported for any of the formulations administered. Geometric mean test/reference individual ratios were: 92.8% for AUC(0-24 h), 93.2% for AUC(0-infinity), 117.2% for Cmax, 131.0% for Ke and 76.2% for T1/2. The variability of Cmax parameter expressed as CV was greater than 25%. Since the 90% CI for AUC(0-24 h) mean ratio were within the 80-125% interval proposed by the Food and Drug Administration, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for the extent of absorption. Since the European Community Agency accepts a 90% CI for Cmax of 70-143%, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for both the rate and the extent of absorption after single dose administration.     

Comparative bioavailability of two fluconazole capsule formulations in healthy volunteers

This work reports the bioavailability of two fluconazole (CAS 86386-73-4) capsule formulations in 24 healthy volunteers of both sexes who received a single oral dose (150 mg). The study was conducted using an open, randomized, two-period crossover design with two-week washout interval. Plasma samples were obtained up to 168 h after drug administration and fluconazole concentration were analyzed using electrospray tandem mass spectrometry coupled to liquid chromatography. The pharmacokinetic parameters obtained for fluconazole after the administration of each formulation included the area under the curve (AUC)(0-168 h), AUC(0-infinity), maximum concentration (Cmax), time to reach Cmax (Tmax), elimination constant (Ke) and half-life (T1/2). The 90% confidence interval for the geometric mean of the individual ratio test formulation/reference formulation were 97.18-108.60% for AUC0-168 h), 90.87-111.11% for AUC(0-infinity), 104.88-114.88% for Cmax 90.38-136.79% for Ke, 91.87-108.93% for T1/2 and (-)1.5-(-)0.10 for Tmax (for individual differences). Since for both Cmax or AUC the 90% CI are within the interval proposed by the Food and Drug Administration (FDA), the test formulation (Zoltrix) is bioequivalent to the reference formulation for both the rate and the extent of absorption after single dose administration.     

Comparative bioavailability of three ibuprofen formulations in healthy human volunteers

OBJECTIVE: To assess the bioequivalence of three ibuprofen formulations (Test formulation: ibuprofen (400 mg capsule) manufactured by Cardinal Health Brasil 402 Ltda. (Sorocaba, Brazil) and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. (SA poundo Paulo, Brazil); Reference formulation (1): ibuprofen (AdvilA(R); 2 A 200 mg coated tablet) from Wyeth-Whitehall Ltda. (Itapevi, Brazil); Reference formulation (2): ibuprofen (AliviumA; 8 ml A 50 mg/ml solution) from Schering Plough S.A. (Rio de Janeiro, Brazil)) in 24 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, three-period crossover design with at least 5-day washout interval. Plasma samples were obtained over a 24-h period. Plasma ibuprofen concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). The following pharmacokinetic parameters were obtained from the ibuprofen plasma concentration vs. time curves: AUC(last), AUC(trunctmax), AUC(inf) and C(max). RESULTS: The limit of quantification for ibuprofen was 0.1 microg A ml(1). The geometric mean with corresponding 90% confidence interval (CI) for Test/Reference (1) percent ratios were 114.24% (90% CI = 105.67, 123.50%) for C(max), 98.97% (90% CI = 94.69, 103.44%) for AUC(last) and 99.40% (90% CI = 95.21, 103.78%) for AUC(inf). The geometric mean and respective 90% confidence interval (CI) for Test/Reference (2) percent ratios were 108.38% (90% CI = 100.19, 117.25%) for C(max), 100.79% (90% CI = 96.39, 105.40%) for AUC(last) and 101.26% (90% CI = 96.94, 105.77%) for AUC(inf); t(max) for the 400 mg Test capsule was shorter than that for the 2 A 200 mg Reference (1) tablets (p < 0.002). Conclusion: Since the 90% CI for AUC(last), AUC(inf) and Cmax ratios were within the 80 - 125% interval proposed by the US FDA, it was concluded that ibuprofen formulation manufactured by Cardinal Health Brasil 402 Ltda. and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. is bioequivalent to the AdvilA and AliviumA formulations with regard to both the rate and the extent of absorption.     

Absolute bioavailability of midazolam after subcutaneous administration to healthy volunteers

AIMS: Midazolam is given intravenously for induction of anaesthesia and conscious sedation and by subcutaneous infusion in patients in palliative care units. The objective of the present study was to determine the absolute bioavailability of subcutaneous midazolam and its pharmacokinetics in young, healthy, male volunteers. METHODS: Eighteen volunteers were given single doses of 0.1 mg kg-1 midazolam i.v. and s.c. after a wash-out period of 7-15 days in an open-label, randomized, cross-over study. Blood samples were collected up to 12 h post-infusion. Plasma concentrations of midazolam and of its two metabolites, 1'-OHM and 4-OHM, were assessed using an h.p.l.c.-MS method (LOQ 0.5 ng ml-1 for each analyte). Vital signs, cardiac parameters and oximetry were monitored. Local tolerance was determined and adverse events were also monitored. RESULTS: After s.c. infusion t(max) and C(max) were 0.51 +/- 0.18 h and 127.8 +/- 29.3 ng ml-1 (mean +/- s.d.), respectively. No statistically significant difference was detected in AUC(0, infinity ) after i.v. and s.c. administration. The mean (+/- s.d.) absolute bioavailability of subcutaneous midazolam was 0.96 (+/- 0.14) (CI 0.84, 1.03). Mean (+/- s.d.) t1/2 was similar after s.c. (3.2 (+/- 1.0) h) and i.v. infusion (2.9 (+/- 0.7) h), although a statistically significant difference was reached (P < 0.05). Mean CL and V of i.v. midazolam were 4.4 +/- 1.0 ml min-1 kg-1 and 1.1 +/- 0.2 l kg-1 (mean +/- s.d.), respectively. Plasma concentrations of 1'-OHM were higher than those of 4-OHM. Few mild and transient adverse events were noted and there were no clinically significant effects on EEG, blood pressure and laboratory parameters. CONCLUSIONS: This study has shown that subcutaneous midazolam has excellent bioavailability and that administration of midazolam by this route could be preferable when the intravenous route is inappropriate.     

Comparative bioavailability of two cetirizine tablet formulations in Indonesian healthy volunteers

AIM: To compare the bioavailability of two cetirizine tablet (10 mg) formulations (ZyrtecA from UCB Pharma, Spain as a reference formulation and RyvelA from Novell Pharmaceutical Laboratories, Indonesia as a test formulation). MATERIAL AND METHODS: The study was conducted according to an open, randomized, two-period crossover design with a 1-week washout period. Eighteen volunteers participated and all completed the study successfully. Blood samples were obtained prior to dosing and at 0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 and 30 hours after drug administration. Plasma concentrations of cetirizine were monitored using high-performance liquid chromatography over a period of 30 hours after administration. The pharmacokinetics parameter AUC(0-30h), AUC(0-infinity) and C(max) were tested for bioequivalence after log-transformation of data and ratios of t(max) were evaluated non-parametrically. RESULT: The point estimates and 90% confidence intervals for AUC(0-30h), AUC(0-infinity) and C(max) were 108.23% (101.90 a 114.95%), 108.11% (101.91 a 114.68%) and 99.71% (90.18 a 110.25%), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products an the US Food and Drug Administration guidelines. CONCLUSION: These results indicate that two medications of cetirizine are bioequivalent and, thus, may be prescribed interchangeably.     

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.     

Comparative bioavailability study with two chlorpropamide tablet formulations in healthy volunteers

OBJECTIVE: The aim of this study was the assessment of the bioequivalence of two formulations (250 mg tablet) of chlorpropamide (CAS 94-20-2) in 36 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval. Plasma samples were obtained over a 72-h period. Plasma chlorpropamide concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the chlorpropamide plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUC(0-72h), AUC(inf) and C(max). RESULTS: The limit of quantification was 0.1 microg/mL for plasma chlorpropamide analysis. The geometric mean and respective 90 % confidence interval (CI) of Test/ Reference percent ratios were 93.99% (87.11%-101.41%) for C(max), 92.45% (85.96%-99.44%) for AUC(0-72h) and 90.30% (83.35%-97.82%) for AUC(0-inf). CONCLUSION: Since the 90 % CI for AUC(0-72h), AUC(0-inf) and C(max) ratios were within the 80-125%interval proposed by the US FDA, it was concluded that chlorpropamide 250 mg tablet (test formulation) was bioequivalent to the reference 250 mg tablet for of both the rate and extent of absorption.     

Comparative bioavailability study with two gemfibrozil tablet formulations in healthy volunteers

OBJECTIVE: To assess the bioequivalence of gemfibrozil (CAS 25812-30-0) 900 mg tablet formulation from EMS Farmaceutica as test formulation versus a 900 mg tablet formulation as reference in 36 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Plasma samples were obtained over a 24-h period. Plasma gemfibrozil concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). From the gemfibrozil plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUClast, AUC(0-inf) and Cmax. RESULTS: The limit of quantification was 0.05 microg/mL for plasma gemfibrozil analysis. The geometric mean and respective 90% confidence interval (CI) of Test/Reference percent ratios were 90.29 (81.39-100.17) for Cmax, 96.26 (90.33-102.59) for AUClast, 96.04 (90.21-102.23) for AUC(0-24 h) and 96.62 (90.82-102.78) for AUC(0-infinity). CONCLUSION: Since the 90% CI for AUClast, AUC(0-inf) and Cmax, ratios were within the 80-125% interval proposed by the U.S. FDA, it was concluded that gemfibrozil 900 mg tablet (test formulation) was bioequivalent to the 900 mg tablet reference formulation for both rate and extent of absorption.     

Pharmacokinetics and bioequivalence study of two digoxin formulations after single-dose administration in healthy Chinese male volunteers

The pharmacokinetics and relative bioavailability/bioequivalence of two formulations of digoxin (CAS 20830-75-5) were assessed in this paper. The study was conducted in 20 healthy Chinese male volunteers according to an open, randomized, single-blind, 2-way crossover study design with a wash-out phase of 14 days. Blood samples for pharmacokinetic profiling were taken up to 72 h post-dose and digoxin plasma concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LCMS/MS) method. Based on the plasma concentration-time data of each individual during two periods, pharmacokinetic parameters, Cmax, AUC0-tau, AUC0-infinity and t1/2, were calculated by applying noncompartmental analysis. Pharmacokinetic data for test and reference formulations were analyzed statistically to evaluate bioequivalence of the two formulations. After oral administration, the values of Cmax Tmax, t1/2, AUC0-tau, AUC0-infinity for test and reference formulations were 2.61 +/- 0.98 and 2.68 +/- 1.09 ng/ mL, 1.0 +/- 0.4 and 1.0 +/- 0.4 h, 27.94 +/- 3.14 and 27.56 +/- 3.86 h, 28.57 +/- 4.99 and 28.77 +/- 6.53 ng x h/mL, 33.44 +/- 4.85 and 33.63 +/- 7.57 ng x h/mL, respectively. Both primary target parameters, AUC0-infinity and AUC0-tau, were tested parametrically by analysis of variance (ANOVA). Relative bioavailabilities were 102.5 +/- 19.2% for AUC0-infinity, 102.0 +/- 19.3% for AUC0-tau. Bioequivalence between test and reference formulations was demonstrated for both parameters, AUC0-infinity and AUC0-tau. The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80%-125%, which means that the test formulation is bioequivalent to the reference formulation of digoxin.