Arzneimittel Forsch
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Arzneimittel Forsch · Jan 2007
Randomized Controlled Trial Comparative StudyPharmacokinetics and bioequivalence study of doxycycline capsules in healthy male subjects.
The aim of the present study was to compare the bioavailability of doxycycline (CAS 564-25-0) from two different doxycycline hyclate (CAS 24390-14-5) capsules (Monodoks 100 mg capsule as test preparation and 100 mg capsule of the originator product as reference preparation) in 24 healthy male subjects. The study was conducted according to an open-label, randomised two-period cross-over design with a wash-out phase of 16 days. Blood samples for pharmacokinetic profiling were taken up to 72 h post-dose, and doxycycline plasma concentrations were determined with a validated HPLC method with UV-detection. ⋯ Plasma elimination half-lives (t1/2) of 16.49 h (test) and 16.75 h (reference) were determined. Both primary target parameters AUC(0-infinity) and Cmax were tested parametrically by analysis of variance (ANOVA) and the 92.39 %-103.53% (AUC(0-infinity)) and 98.45%-111.74% (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 0%-125%.
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Arzneimittel Forsch · Jan 2007
Randomized Controlled TrialPharmacokinetics 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. ⋯ 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%.
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Arzneimittel Forsch · Jan 2007
Randomized Controlled Trial Comparative StudyBioeqivalence assessment of two domperidone 1 tablet formulations.
A randomized, single-dose, crossover study was conducted to assess the bioavailability of two domperidone (CAS 57808-66-9) tablet formulations, Domperidone (test) and a commercially available original preparation (reference) under fasting conditions. A 10 mg dose of each formulation was administered to 36 healthy male volunteers with a one-week washout period, 17 blood samples were collected over 48 h, plasma concentrations of domperidone were analyzed by a locally validated LC-MS-MS assay, and the pharmacokinetic parameters were determined by the standard non-compartmental method. ⋯ ANOVA revealed significant subject's effect for AU4C(0 --> t), AUC((0 -->infinity), C(max), and t1/2 with a ratio of the inter-subject to intra-subject coefficient of variation of 2.10, 1.55, 1.10, and 1.02, respectively. The results indicate that the two formulations are equivalent in relation to the extent and rate of absorption and confirm the previously reported marked intra-individual variations in the pharmacokinetics of domperidone.
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Arzneimittel Forsch · Jan 2007
Randomized Controlled Trial Comparative StudyBioequivalence study of two metformin formulations.
A randomized single-dose cross-over study was conducted on 24 healthy male volunteers to compare the bioavailability of two metformin (CAS 657-24-9) tablet formulations, Emiphage (test) and a commercially available original preparation (reference). A dose of 850 mg was administered after an overnight fast with a washout period of seven days. Eighteen blood samples were collected over 32 h. ⋯ Mean +/- SD maximum concentration (C(max)), time to reach maximum concentration (T(max)), area under the curve (AUC(0 --> t) and AUC(0 --> infinity)), and elimination half-life (t(1/2)) were 1.73 +/- 0.54 and 1.86 +/- 0.67 microg/ml, 2.6 +/- 1.2 and 2.0 +/- 1.0 h, 10.72 +/- 3.93 and 10.82 +/- 3.72 microg x h/ml, 11.53 - 4.14 and 11.6 +/- 3.84 microg x h/ml, and 3.1 +/- 0.7 and 3.1 +/- 0.9 h for the test and reference formulation, respectively. The parametric 90% confidence intervals on the mean of the difference (test - reference) between log-transformed values of the two formulations were 82.92% to 98.78%, 85.95% to 101.47%, and 77.82% to 100.4% for AUC(0 --> t), AUC(0 --> infinity), and C(max), respectively. The results indicate that the two formulations can be considered equivalent in the extent of absorption under fasting conditions.
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Arzneimittel Forsch · Jan 2007
Randomized Controlled Trial Multicenter Study Comparative Study[Comparative clinical study of two dexamethasone phosphate-containing ophthalmics].
For the drug application of the already known active ingredient dexamethasone dihydrogen phosphate disodium salt (CAS 2392-39-4) for ocular use clinical data on the efficacy and safety were required by the drug regulatory agency. The comparison of the pharmaceutical properties had already shown that no differences in clinical use had to be expected. The results of a double-blind, randomised, comparative clinical study on 210 patients prove that no differences between test and comparator product could be observed. This case shows that the demand for clinical trials to proof therapeutic equivalence should be done with a sense of proportion related to the specific situation.