Bioequivalence study of two amoxicillin formulations

A randomized single-dose crossover study was conducted in 24 healthy male volunteers to compare the bioavailability of two amoxicillin (CAS 26787-78-0) formulations, Glomox tablet (test) and a commercially available original preparation, amoxicillin capsule (reference). One thousand milligram of each formulation were administered after an overnight fast with a washout period of three days. Sixteen blood samples were collected over 10 h, amoxicillin concentrations in deproteinized serum were determined by a high performance liquid chromatographic (HPLC) assay, and pharmacokinetic parameters were analyzed by the standard non-compartmental method. Mean +/- SD maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under the curve (AUC0-->t and AUC0-->infinity), and elimination half-life (t1/2) were 13.30 +/- 4.52 and 12.99 +/- 3.56 microg/ml, 1.92 +/- 0.76 and 2.02 +/- 0.62 h, 42.50 +/- 13.62 and 42.24 +/- 12.35 microg x h/ml, 46.31 +/- 13.23 and 46.08 +/- 12.14 microg x h/ml, and 1.54 +/- 0.39 and 1.48 +/- 0.48 h for the test and reference formulation, respectively. The parametric 90 % confidence intervals of the mean of the difference (test-reference) between log-transformed values of the two formulations were 92.61% to 109.50%, 92.83% to 109.12%, and 93.11% to 109.41% for AUC0-->t, AUC0-->infinity, and Cmax, respectively. The results indicate that the two formulations can be considered equivalent with regard to the rate and extent of absorption under fasting conditions.     

Comparative bioavailability of two oral L-thyroxine formulations after multiple dose administration in patients with hypothyroidism and its relation with therapeutic endpoints and dissolution profiles

The aim of the present study was to evaluate the bioequivalence and therapeutic equivalence of the two most commonly prescribed L-thyroxine (monsodium L-thyroxine hydrate, CAS 25416-65-3) formulations in Brazil in patients treated for hypothyroidism. Twenty-four patients received 100 micrograms L-thyroxine daily of either Puran T4 (test) or the Brazilian reference formulation (reference) during 42 days, in a two-period crossover design. Serum samples obtained over a 24-h interval were analyzed for their total T4 concentration by a chemiluminescent immunoassay. Content and uniformity of the tablets and dissolution studies were also assessed according to USP 24 monograph using an isocratic HPLC-UV system and a rotating-paddle method. The mean pharmacokinetic parameters for total T4, expressed as geometric means (CV), for the test and reference were, respectively: Cmax (microgram/dl) 9.8 (14.3%) and 10.8 (14.9%); AUC0-24 h (microgram/dl.h) 206.8 (13.9%) and 230.4 (14.9%). Median values (90% CI) for Tmax (h) were 3 (2-3) and 2 (2-4) for the test and reference, respectively. 90% CI for ratios of LogCmax and LogAUC0-24 h were 86.6-94.9 and 86.3-93.4, respectively. Although the test exhibited values of Cmax and AUC0-24 h around 10% lower than the reference, these formulations must be considered bioequivalent since the 90% CI for both Cmax and AUC0-24 h mean ratio were within the 80-125% interval as proposed by the US Food and Drug Administration and the Brazilian legislation. TSH dosages within the normal range further support therapeutic equivalence between the two formulations. Dissolution data were roughly in agreement with in vivo results since both formulations comply with the USP dissolution criteria although the test tablets had a slower dissolution rate than the reference tablets. As a conclusion, the two oral formulations of L-thyroxine are both bioequivalent and therapeutically equivalent although presenting a small difference in their extent of absorption. Noteworthy, the dissolution profiles of the tablets correlate well with their bioavailability in the present experimental conditions.     

Bioequivalence of two oral formulations of triflusal capsules in healthy volunteers

Triflusal (CAS 322-79-2) is an antiplatelet agent related to salicylates used in several European and Latin American countries in the treatment of cardiovascular diseases. The aim of this paper was to evaluate the bioequivalence of triflusal derived from two preparations using both parent drug and metabolite pharmacokinetic data. The bioavailabolity was measured in 24 healthy male Caucasian volunteers following a single oral dose (600 mg) of the test or reference products in the fasting state. Blood samples were collected for 120 h. Plasma concentrations of triflusal and its metabolite 3-hydroxy-4-trifluoromethylbenzoic acid (HTB) were analyzed by high-performance liquid chromatography with UV and fluorescence detection, respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax, AUC0-t and AUC0-infinity were tested for bioequivalence using ANOVA and Schuirmann's two-one sided t-test. Tmax was analyzed by nonparametric pharmacokinetic parameters of triflusal and HTB derived from the two formulations were nearly consistent with previous observations. Triflusal parameters derived from the test and reference drug were as follows: Cmax (16.85 +/- 11.41 vs 14.48 +/- 7.22 mg/l), AUC0-t (18.43 +/- 10.91 vs 16.22 +/- 7.58 mg/l per hour), Tmax (1 range 0.25-2h vs 0.875 range 0.25-1.5 h), and t(1/2) (0.49 +/- 00.27 vs 0.76 +/- 0.64). HTB parameters after test and reference formulation administration were as follows: Cmax (68.13 +/- 23.05 vs 65.51 +/- 19.44 mg/l), AUC0-t (2748.18 +/- 971.91 vs 2877.97 +/- 881.2 h x mg/l), AUC0-infinity (3350.15 +/- 1182.62 vs 3372.49 +/- 1110.35 h x mg/l), Tmax (2 range 1-10 h vs 2 range 0.75-12 h), and t(1/2) (42.19 +/- 7.82 vs 43.13 +/- 6.56 h). 90% of confidence intervals for the test/reference ratio of Cmax AUC0-t and AUC0-infinity derived from both triflusal and HTB were found within the range of 80%-125% acceptable for bioequivalence. No significant difference was found between the Tmax values for triflusal and HTB. It was concluded that the two preparations are bioequivalent and may be prescribed interchangeably.     

Bioequivalence evaluation of two rosiglitazone tablet formulations

A randomized, two-period, two-sequence, crossover study was conducted on 28 healthy male volunteers to compare the bioavailability of two rosiglita-zone (CAS 122320-73-4) tablet formulations, a test and a commercially available original preparation (reference), under fasting conditions. The two preparations were given in a dose of 8 mg with a 7-day washout period between the two preparations. Eighteen blood samples were collected over 24 h, plasma rosiglitazone concentrations were determined by locally validated high performance liquid chromatography (HPLC) assay, and pharmacokinetic parameters were analyzed by the standard non-compartmental method. The mean+/-SD of AUC0-->t, AUC0-->infinity, Cmax, Tmax, and t1/2 were 4.80+/-1.89 and 4.76 +/-1.94 microg x h/ml, 5.17+/-2.11 and 5.08 +/- 2.27 microg x h/ml, 0.93+/-0.24 and 0.99+/-0.34 microg/ml, 1.0 +/-0.4 and 0.8+/-0.5 h, and 5.0+/-2.0 and 5.0+/-2.0 h for the test and reference formulation, respectively. ANOVA did not show significant formulation, period, or sequence effect for any of the pharmacokinetic parameters. The 90 % confidence intervals of the mean differences between log-transformed values of the two formulations were 93.09 % to 109.73 %, 94.04 % to 111.70 %, and 89.70 % to 103.24 % for AUC0-->t, AUC-->infinity, and Cmax, respectively. It is concluded that the two formulations are equivalent in relation to the rate and extent of absorption.     

Bioequivalence study of two oral formulations of cefadroxil in healthy volunteers

Two different cefadroxil (CAS 50370-12-2) formulations were evaluated for their relative bioavailability in 24 healthy volunteers who received a single 500 mg oral dose of each preparation. An open, randomized clinical trial designed as a two-period crossover study with a 7-day washout period between doses was employed. Plasma samples for assessments of their cefadroxil concentration by HPLC-UV were obtained over 8 h after administration. Values of 48.94 +/- 10.18 pg x h/ml for test, and 48.51 +/- 9.02 microg x h/ml for the reference preparation AUC(0-t) demonstrate a nearly identical extend of drug absorption. Maximum plasma concentration Cmax of 16.04 +/- 4.94 microg/ml and 16.01 + 4.02 microg/ml achieved for the test and reference preparations did not differ significantly. The parametric 90% confidence intervals (CI) of the mean of the difference (test-reference) between log-transformed values of the two formulations were 96.80% to 104.51% and 92.01% to 107.00% for AUC(0-t) and Cmax, respectively. Since for both AUC(0-t) or Cmax the 90% CI values are within the interval proposed by the Food and Drug Administration, the test product is bioequivalent to the reference product for both the rate and extent of absorption after single dose administration.     

Comparison of two microemulsion of cyclosporine A in healthy volunteers

This study evaluated the bioequivalence of a new Cyclosporine A microemulsion formulation in comparison to the reference market standard. Twenty-four adult healthy volunteers were randomised to receive the two Cyclosporin A microemulsion formulations, at a dose of 2.5 mg/kg, according to a cross-over design. Blood samples were taken before drug administration and at 12 points within 24 hours. Cyclosporine A whole blood concentrations were determined by HPLC. The pharmacokinetic parameters AUC0-t and AUC0-infinity were calculated by the trapezoidal rule, Cmax and Tmax were obtained directly from blood data. AUCs and Cmax were tested for bioequivalence after log transformation of data, differences for Tmax were evaluated by the rank test of Wilcoxon for paired data. The 90% confidence interval ratio between tested/reference drug was 0.98 for AUC0-t, 0.96 for AUC0-infinity and 1.01 for Cmax. All of them were within the range of bioequivalence. Tmax was 1.60 +/- 0.44 hours after test drug and 1.67 +/- 0.48 after reference drug (p = 0.27, Wilcoxon test). According to these results the two Cyclosporine A microemulsion formulations can be considered bioequivalent.     

Bioequivalence assessment of two capsule formulations of omeprazole in healthy volunteers

A randomized, single-dose, crossover study was conducted to assess the bioavailability of two omeprazole (CAS 73590-58-6) capsule formulations, Emilok (test) and a commercially available original preparation (reference), under fasting conditions. A 20 mg dose of each formulation was administered to 36 healthy male volunteers with one-week washout period, 17 blood samples were collected over 12 h, plasma omeprazole concentrations were determined by a locally validated high performance liquid chromatography (HPLC) assay, and omeprazole pharmacokinetic parameters were analyzed by the standard non-compartmental method. Mean +/- SD of Cmax, Tmax, AUC(0 --> t), AUC(0 --> infinity), and t1/2 were 0.41 +/- 0.21 and 0.48 +/- 0.27 microg/ml, 1.98 +/- 1.02 and 1.63 +/- 0.78 h, 0.95 +/- 0.78 and 1.00 +/- 0.90 microg x h/ml, 0.99 +/- 0.81 and 1.04 +/- 0.95 microg x h/ml, and 1.30 +/- 0.64 and 1.14 +/- 0.61 h for the test and reference formulations, respectively. The parametric 90% confidence intervals on mean difference between log-transformed values of the two formulations were within the acceptable bioequivalence range of 80% to 125% for AUC(0 --> t) and AUC(0 --> infinity) (88.63% to 104.98%, and 91.71% to 106.86%, respectively) but not for Cmax (76.27% to 103.63%). ANOVA revealed significant subject's effect for AUC(0 --> t), AUC(0 --> infinity), Cmax, and t1/2 with a ratio of the inter-subject to intra-subject coefficient of variation of 3.66, 3.92, 1.25, and 1.46, respectively. The results confirm the presence of marked individual variations in the pharmacokinetics of omeprazole and indicate that the two formulations are equivalent in relation to the extent but not the rate of absorption.     

Bioequivalence studies of 2 oral cefaclor capsule formulations in chinese healthy subjects

An open-label, single-dose, randomized, crossover study was carried out in 20 Chinese healthy male subjects to compare the pharmacokinetics of 2 cefaclor (CAS 53994-73-3) formulations after administration of a single 250 mg dose of each drug with a 1-week wash-out period. Blood samples were collected before and with 6 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detector. 2 formulations were evaluated using the following pharmacokinetic parameters: AUC0-t, Cmax and tmax was analyzed nonparametrically. The 90% confidence interval (CI) of the ratios (teat/reference) of log-transformed AUC0-t and Cmax fell within the bioequivalence acceptance range of 80-125%. The results showed that the 90% CI of the ratios of AUC0-t and Cmax were 105.1% (101.0-109.4%) and 92.4% (82.5-103.4%), respectively, which therefore could conclude 2 oral cefaclor capsule formulations of cefaclor are bioequivalent. Both treatments showed similar tolerability and safety.     

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.     

Bioequivalence of two lamivudine tablet formulations

The present study describes the determination of the bioavailability of a new commercial tablet formulation of lamivudine (CAS 134678-17-4) compared with a reference formulation. The comparative bioequivalence of the test and a reference formulation (each 3 x 150 mg) was assessed in 24 healthy volunteers by means of a randomized two-way crossover design. Prior to the study both the test and reference formulations were examined for conformation to chromatographic purity and drug content. Each volunteer received the test (T) and the reference formulation (R) with a one-week drug-free interval between administrations. The plasma concentrations of T were monitored over a period of 12 h after drug administration using a sensitive HPLC method. Pharmacokinetic parameters for T were determined from plasma concentration-time data. Statistical tests were carried out at 90% confidence intervals using a parametric method (three-way ANOVA) for AUC and Cmax, and non-parametric method for Tmax. The present study showed that both formulations were bioequivalent for the geometric mean of AUC(0-12), AUC0-infinity), Cmax, and Tmax at the 90% confidence interval. The bioavailability of the test (%) was 96.7, 93.3, 99.7, 100.3, respectively. The T:R ratio was, in each case, well within the acceptable range of 100 +/- 20%.     

Comparative bioavailability of two oral formulations of bromazepam in healthy volunteers.

The aim of this study was to assess the pharmacokinetic profile of two bromazepam (CAS 1812-30-2) formulations in 24 healthy volunteers. An open, randomised clinical trial designed as two-period crossover with 14-day washout between doses was employed. Plasma samples for assessments of their bromazepam concentration by HPLC-UV were obtained over 96 h after administration. No adverse effect was reported for any of the formulations administered. The following pharmacokinetics parameters were calculated: AUC(0-96 h), AUCinf, Cmax, Tmax, Ke and T1/2. The 90% confidence intervals (CI) for the mean test/reference individual ratios were 81-109 for AUC and 84-116 for Cmax. Since the 90% CI for both, AUC and Cmax ratios were within the 80-125% interval proposed by the Food and Drug Administration, it is concluded that the new bromazepam slow-release formulation is therapeutic equivalent to the conventional formulation for both, the extent and the rate of absorption after single dose administration in healthy volunteers.     

Plasma tenoxicam concentrations after single and multiple oral doses

The pharmacokinetics of single- and multiple-dose administration of tenoxicam 20 mg were evaluated in 8 healthy males. Maximum plasma concentration (Cmax) after the first dose was 2.76 +/- 0.48 micrograms/ml (mean +/- s.d.) and the time to reach Cmax (Tmax) was 5.0 +/- 3.0 h. The area under the plasma concentration-time curve (AUC0-infinity) after a single administration of tenoxicam was 242.5 +/- 73.5 micrograms x h/ml. The elimination half-life (t1/2) was 66.3 +/- 15.8 h and the plasma concentration at 24 hours after dosing (Cmin) was 1.84 +/- 0.33 micrograms/ml. Steady-state plasma concentrations of tenoxicam were virtually reached after 10 consecutive daily doses. At steady-state, Cmax averaged 13.63 +/- 3.33 micrograms/ml and Tmax remained 5.0 +/- 3.0 hours. AUC within a dosing interval at steady-state was 262.2 +/- 67.0 micrograms x h/ml, Cminss was 9.67 +/- 3.25 micrograms/ml, and t1/2 averaged 74.2 +/- 13.3 h. The average fluctuation during multiple-dose administration was 26.8 +/- 8.0% and the accumulation ratio was 5.82 +/- 0.60. Steady-state pharmacokinetic parameters predicted from the first-dose data slightly underestimated observed values, but the results supported the assumption of linear pharmacokinetics during multiple-dose tenoxicam administration.     

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.     

Bioequivalence study of two esomeprazole enteric coated formulations in healthy Chinese volunteers

A bioequivalence study of two esomeprazole (CAS 119141-88-7) enteric-coated formulations was carried out in 20 healthy Chinese volunteers according to a single dose, two-sequence, crossover randomized design. The two formulations were administered in two treatment days, separated by a washout period of 7 days. Blood samples were collected at specified time intervals over 10 h post-dosing. Plasma samples were separated and assayed for esomeprazole using a selective and sensitive HPLC method with UV detection. The pharmacokinetic parameters AUC(0-12h), AUCmax, Cmax, tmax, t1/2 and MRT were determined from the plasma concentration-time profile of both formulations. ANOVA and two one-sided t-test procedures showed no significant difference in log-transformed Cmax, AUC(0-12h) and AUC(0-infinity) while the 90% confidence interval (CI) of the ratio of the geometric means of their values were also used to assess bioequivalence between the two formulations. The results of this study indicated that the two esomeprazole formulations can be considered to be bioequivalent.     

Relative bioavailability of three cefixime formulations

Three galenic formulations of cefixime (tablet, syrup and dry suspension) containing 200 mg each were compared with respect to their relative bioavailability in twelve healthy volunteers. All three formulations showed reliable absorption. Mean peak plasma concentrations were reached after 3.3-3.5 h, mean terminal half lives were 2.9-3.1 h. 18-24% of the dose administered were recovered unchanged in the urine. Best bioavailability was obtained with the dry suspension (AUC0-infinity = 25.8 +/- 7.0 micrograms/ml h; Cmax = 3.4 +/- 0.9 microgram/ml), followed by the tablet (AUC0-infinity = 20.9 +/- 8.1 micrograms/ml h; Cmax = 3.0 +/- 1.0 micrograms/ml) and the syrup which is based on triglycerides (AUC0-infinity = 17.8 +/- 5.9 micrograms/ml h; Cmax = 2.4 +/- 0.7 micrograms/ml). The statistical analysis resulted in bioinequivalence between dry suspension and syrup. It is concluded that best bioavailability of cefixime after oral administration is guaranteed when taken in an "aqueous medium" either as dry suspension or as tablet with "plenty of liquid".     

Bioequivalence assessment of two different tablet formulations of diltiazem after single and repeated doses in healthy subjects

The study was performed on 14 healthy volunteers in order to compare the pharmacokinetics and hence assess the bioequivalence of two different tablet formulations of diltiazem administered orally. The study was carried out after single doses (60 mg) and repeated doses (60 mg three times a day for six days and 60 mg on the seventh day) according to a randomised, cross-over, open design. The pharmacokinetic parameters AUC0-infinity (ng h/ml), Tmax(h) and Cmax (ng/ml) were calculated for the two formulations after a single dose, while AUCt1-t2 (= AUC for a repetitive dose interval or dosing cycle, ng h/ml) and PTF (peak trough fluctuation) were calculated after repeated doses. The bioequivalence assessment was the shortest 90% confidence interval for the ratio (difference) of expected medians in the respective bioequivalence range (0.80-1.20). The results of this study show that, after either a single dose or repeated doses of test or reference formulations of diltiazem, the pharmacokinetics of the two formulations are similar. The ratios of AUC on day 1 (for single-dose treatment) and on day 7 (for repeated-dose treatment), and the corresponding 90% confidence intervals demonstrate bioequivalence between the two formulations of diltiazem within the accepted range of 0.80-1.20 (80-120%).     

Bioequivalence study of two limaprost alfadex 5 microg tablets in healthy subjects: moisture-resistant tablet (dextran formulation) versus standard tablet (lactose formulation)

OBJECTIVE: A study was conducted to assess the bioequivalence of two limaprost alfadex 5 microg tablets, a moisture-resistant tablet (dextran formulation) and a standard tablet (lactose formulation). MATERIALS AND METHODS: The clinical investigation was designed as a randomized, open-labeled, two-part, two-treatment, two-period crossover study, in 120 healthy male volunteers. One tablet of either formulation was administered with 200 ml of water after 10-hour overnight fast. After dosing, serial blood samples were collected for a period of 6 hours. Plasma harvested from blood was analyzed for limaprost by a validated LC/MS/MS method. The peak plasma concentration (Cmax) values and time associated with the maximal concentration (tmax) were obtained from the observed data. The elimination rate constant (lambda z) was obtained as the slope of the linear regression of the log-transformed concentration values vs. time data in the terminal phase, and the elimination half-life (t1/2) was calculated as 0.693/lambda z. The area under the curve to the last measurable point (AUC0-t) was estimated by the linear trapezoidal rule. The analysis of variance (ANOVA) was carried out using log-transformed AUC0-t, AUC0-A yen and Cmax and untransformed tmax, and 90% confidence intervals for AUC0-t and Cmax were calculated. If the 90% confidence intervals (CI) for both AUC0-t and Cmax fell fully within the interval 80 - 125%, the bioequivalence of the two formulations was established. RESULTS: The means of AUC0-t were 0.779 vs. 0.754 pg x h/ml (test vs. reference), and the means of the Cmax were 1.26 vs. 1.12 pg/ml (test vs. reference). The geometric mean ratios of the test formulation to reference formulation for AUC0-t and Cmax were 104.0 and 112.4%, respectively, and the 90% CI for AUC0-t and Cmax were 100.7 - 107.4% and 105.6 - 119.6%, respectively. Both 90% CI for AUC0-t and Cmax fell within the Ministry of Health, Labour and Welfare of Japan accepted bioequivalence range of 80 - 125%. CONCLUSIONS: Based on the results, the moisture-resistant tablet was determined to be bioequivalent to the standard tablet.     

Bioequivalence and pharmacokinetics of 70 mg alendronate sodium tablets by measuring alendronate in plasma

The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a 2x2 crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma concentration-time curve from time 0 to the last sampling time at 7 h (AUC(0-7h) was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration (Cmax) and the time to reach Cmax (Tmax) were derived from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed AUC(0-7h) and Cmax, and untransformed Tmax. For the test medication versus the reference medication, the AUC(0-7h) were 87.63 +/- 29.27 vs. 102.44 +/- 69.96 ng x h x mL(-1) and the Cmax values were 34.29 +/- 13.77 vs. 38.47 +/- 24.39 ng x mL(-1), respectively. The 90% confidence intervals of the mean differences of the logarithmic transformed AUC(0-7h) and Cmax values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the U.S. Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: t(1/2), 1.87 +/- 0.62 vs. 1.77 +/- 0.54 h; V/F, 2061.30 +/- 986.49 vs. 2576.45 +/- 1826.05 L; CL/F, 835.32 +/- 357.35 vs. 889.48 +/- 485.87 L x h(-1); K(el), 0.42 +/- 0.14 vs. 0.40 +/- 0.18 h(-1); Ka, 4.46 +/- 3.63 vs. 3.80 +/- 3.64 h(-1); and Tlag, 0.19 +/- 0.09 vs. 0.18 +/- 0.06 h. These results indicated that two alendronate formulations (70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.     

Comparative bioavailability of two brands of atenolol 100 mg tablets (Tensotin and Tenormin) in healthy human volunteers

A bioequivalence study of two oral formulations of 100 mg atenolol was carried out in 24 healthy volunteers following a single dose, two-sequence, cross-over randomized design at the International Pharmaceutical Research Centre (IPRC), as a joint venture with Al-Mowasah Hospital, Amman, Jordan. The two formulations were Tensotin (Julphar, UAE) as test and Tenormin (Zeneca, UK) as reference product. Both test and reference tablets were administered with 240 ml of water to each subject after an overnight fast on 2 treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 36 h. Whole blood was analysed for atenolol by a sensitive, reproducible and accurate HPLC method with fluorescence detection capable of detecting atenolol in the range of 20-1600 ng/ml with a limit of quantitation of 20 ng/ml. Various pharmacokinetic parameters including AUC0-t, AUC0-proportional to), Cmax, Tmax, T1/2 and lambdaZ were determined from blood concentrations of both formulations and found to be in good agreement with reported values. AUC0-t, AUC0-proportional to), and Cmax were tested for bioequivalence after log-transformation of data using ANOVA and 90% confidence interval and were found within the acceptable range of 80%-125%. Based on these statistical inferences, it was concluded that Tensotin is bioequivalent to Tenormin.     

Bioequivalence study of a generic quetiapine in healthy male volunteers

Aim: To study the bioequivalence of a generic quetiapine (Quantia 200(R), manufactured by the Unison Laboratories Co., Ltd., Bangkok, Thailand) and the innovator product (Seroquel(R), AstraZeneca, Macclesfield, UK). Volunteers and methods: The study was a randomized, 2-way crossover design with a 2-week washout period in 24 healthy Thai male volunteers. After a single 200 mg oral dosing, serial blood samples were collected at appropriate interval up to 48 h. Plasma quetiapine concentrations were determined by high-performance liquid chromatography (HPLC). Pharmacokinetic parameters were estimated using the WinNonlin(R) software with noncompartment model analysis. Comparative bioequivalence between the two formulations was determined by analysis of variance (ANOVA) for 2-way crossover design. Results: The mean +/- SD of maximum plasma concentration (Cmax), the area under the plasma concentration-time curve from 0 - 48 h (AUC0-48) and the area under the plasma concentration-time curve from 0 to infinity (AUC0-inf) of Quantia 200(R) vs. Seroquel(R) were 886.60 +/- 356.50 vs. 811.34 +/- 323.37 ng/ml; 3,754.41 +/- 1,453.00 vs. 3,420.00 +/- 1,229.6 ng x h/ml and 4,015.35 +/- 1,528.25 vs. 3,769.45 +/- 1,296.69 ng x h/ml, respectively. Time to reach Cmax (tmax) of Quantia 200(R) and Seroquel(R) were 1.08 +/- 0.778 and 1.10 +/- 0.79 h, respectively, and thus not significantly different. The 90% confidence interval of the ratios of the logarithmically transformed of Cmax, AUC0-48 and AUC0-inf were 98.21 - 124.37%, 94.43 - 117.03% and 94.77 - 116.61%, respectively, which were within the acceptable range of 80 - 125%. Power of the test for Cmax, AUC0-48 and AUC0-inf was 92.1%, 96.9% and 97.4%, respectively. Conclusion: Quantia 200(R), used in this study, was bioequivalent to Seroquel(R) in terms of both the rate and extent of absorption.