Arzneimittel Forsch
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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 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 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 Comparative StudyPharmacokinetics and bioequivalence study of ranitidine film tablets in healthy male subjects.
The aim of the present study was to compare the bioavailability of ranitidine (CAS 66357-35-5) from two different ranitidine hydrochloride (CAS 66357-59-3) film tablets (Ranitab 150 mg film tablets as test preparation and 150 mg film tablets of the originator product as reference preparation). The study was conducted according to an open-label, randomised two-period cross-over design with a wash-out phase of 9 days. Blood samples for pharmacokinetic profiling were taken up to 24 h post-dose, and ranitidine plasma concentrations were determined with a validated HPLC method with UV-detection. ⋯ Plasma elimination half-lives (t1/2) of 2.78 h (test) and 2.89 h (reference) were determined. Both primary target parameters AUC(0-infinity) and Cmax were tested parametrically by analysis of variance (ANOVA) and the 90% confidence intervals were between 91.93 %-106.98 % (AUC (0-infinity) and 92.34%-118.85% (Cmax). Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90 % confidence intervals of the T/R ratios of logarithmically transformed data were in the generally accepted range of 80 %-125 %.
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Arzneimittel Forsch · Jan 2007
Effect of benidipine hydrochloride, a long-acting T-type calcium channel blocker, on blood pressure and renal function in hypertensive patients with diabetes mellitus. Analysis after switching from cilnidipine to benidipine.
Calcium channel blockers are commonly used to treat hypertension, and are known to generally act on the L-type calcium channel. Recent studies have shown, however, that some calcium channel blockers also block other calcium channel subtypes, including N- and T-type channels. Cilnidipine (CAS 132203-70-4) is an L- and N-type calcium channel blocker, and benidipine hydrochloride (benidipine, CAS 91599-74-5) is known to inhibit the T-type as well as L- and N-type calcium channels. In this study, effects of switching from cilnidipine to benidipine on blood pressure (BP) lowering and renal functions were investigated in order to clarify the physiological properties of the T-type calcium channel. ⋯ These results demonstrate that benidipine has a more potent antihypertensive effect than cilnidipine and also a renoprotective effect, indicating the high usefulness of benidipine in hypertensive patients with diabetes. T-type calcium channel blockade was suggested to be possibly involved in the enoprotective effect of benidipine.