Arzneimittel Forsch
-
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%.
-
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.
-
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.
-
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.
-
Arzneimittel Forsch · Jan 2007
Randomized Controlled TrialBioequivalence study of a sustained release fixed dose combination capsule containing esomeprazole and domperidone in healthy subjects.
The study was designed to determine the relative bioavailability of two sustained release fixed dose combination (FDC) products of two manufacturers containing esomeprazole (CAS 326602-80-6) 40 mg and domperidone (CAS 57808-66-9) 30 mg in 24 healthy male volunteers. The pharmacokinetics of esomeprazole and domperidone individually after oral administration of tablet formulation has been extensively evaluated in adult volunteers. However, no published data are available regarding the combined pharmacokinetics and bioavailability of this particular FDC. ⋯ These findings clearly indicate that the two products are bioequivalent in terms of rate and extent of drug absorption. Both preparations were well tolerated with no adverse reactions throughout the study.