Arzneimittel Forsch
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Arzneimittel Forsch · Jan 2010
Randomized Controlled Trial Comparative StudyBioequivalence study of a fixed dose combination tablet containing rabeprazole and diclofenac sodium in healthy Indian subjects.
The pharmacokinetics of rabeprazole (CAS 117976-89-3) and diclofenac sodium (CAS 15307-79-6) has been extensively evaluated in adult human volunteers individually after oral administration of tablet formulation. However, no published data is available regarding the combined pharmacokinetics and bioavailability of this particular fixed dose combination. In light of the above, a clinical study was designed to evaluate the bioequivalence of two fixed dose combination (FDC) products (reference and test) of two manufacturers containing rabeprazole 20 mg and diclofenac sodium 100 mg slow release (SR) tablet in healthy Indian male volunteers. ⋯ The results of this study indicated that there were no statistically significant differences between the logarithmically transformed AUC(0-infinity) and Cmax values of the two preparations. The 90% confidence interval for the ratio of logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limit of 0.80-1.25 and the relative bioavailability of rabeprazole and diclofenac sodium were found to be 98.6% and 98.9% respectively in the test product. Thus, these findings clearly indicated that the two products are bioequivalent in terms of rate and extent of drug absorption.
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Arzneimittel Forsch · Jan 2010
Randomized Controlled TrialBioequivalence studies of two different film-coated tablet formulations of valacyclovir of two different strengths in healthy volunteers.
These studies were conducted in order to assess the bioequivalence of two film-coated formulations containing 250 mg and 1000 mg of valacyclovir (INN: valaciclovir; CAS 124832-26-4), which is the L-valyl ester and a pro-drug of the antiviral drug acyclovir (INN: aciclovir). In the study with valacyclovir 250 mg, 36 healthy subjects were enrolled in a randomized, single-dose, open-label, 2-way crossover study, with a washout period of 10 days. In the study with valacyclovir 1000 mg, 46 healthy subjects were enrolled in a randomized, single-dose, open-label, 2-way crossover study, with a washout period of 7 days. ⋯ In the study with valacyclovir 1000 mg formulations, the 90% confidence intervals obtained for valacyclovir were 93.20-107.35% for C(max), 90.87-96.27% for AUC(0-inf) and 90.87-96.27% for AUC(0-t) whereas for acyclovir the 90% CIs obtained were 95.98-104.94% for C(max), 97.13-103.94% for AUC(0-inf) and 97.14-104.09% for AUC(0-t). All the 90% confidence intervals obtained for all the parameters assessed were within the predefined range (80-125%). Based on these results, it can be concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption.
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Arzneimittel Forsch · Jan 2010
Efficacy and safety of ferric carboxymaltose in correcting iron-deficiency anemia: a review of randomized controlled trials across different indications.
Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD). In most trials, patients received either FCM doses of < or = 1000 mg, administered intravenously (i.v.) over < or = 15 min. or oral ferrous sulfate (FeSulf) 325 mg (65 mg iron), three times daily (t.i.d.), or 304 mg (100 mg iron), twice daily (b.i.d.). In one trial, patients on HD received 200 mg i.v. of either FCM or iron sucrose (ISC), two-to-three times weekly. ⋯ Safety data from more than 3000 patients showed that FCM was well tolerated. No safety concerns have been identified in breastfed infants of mothers receiving FCM. FCM is, therefore, an effective and well-tolerated option in the treatment of IDA.
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Arzneimittel Forsch · Jan 2010
Randomized Controlled Trial Comparative StudyBioequivalence study of two different tablet formulations of donepezil using truncated areas under the curve. A single-center, single-dose, randomized, open-label, 2-way crossover study under fasting conditions.
Donepezil hydrochloride (CAS 120014-06-4) is a piperidine-based, reversible inhibitor of the enzyme acetylcholinesterase (AChE). It is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine (ACh) through reversible inhibition of its hydrolysis by AChE. ⋯ Bioequivalence between test and reference formulations, both in terms of rate and extension of absorption, under fasting conditions, was concluded according to European guidelines. Both formulations were well tolerated. The conclusion of bioequivalence was also supported using the truncated AUCs approach.
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Arzneimittel Forsch · Jan 2010
Pharmacodynamics and safety of ferric carboxymaltose: a multiple-dose study in patients with iron-deficiency anaemia secondary to a gastrointestinal disorder.
This multiple-dose Phase I/II study provided pharmacodynamics and pharmacokinetics data on the therapeutic benefit of ferric carboxymaltose (FCM, Ferinject) and evaluated the safety and tolerability of this intravenous (i.v.) iron preparation. Two doses of iron as FCM were given as i.v. infusion over 15 min, 500 mg iron given once weekly for up to 4 weeks (Cohort 1) or 1000 mg iron weekly for 2 weeks (Cohort 2), in patients with a total requirement > or = 1000 mg iron (total cumulative maximum dose < or = 2000 mg iron). Adults with moderate to severe, stable iron-deficiency anaemia (IDA) (haemoglobin [Hb] < or = 11.0 g/dl, serum ferritin < 100 microg/l, transferrin saturation [TSAT] < 16%) due to a gastrointestinal (GI) disorder were included. ⋯ Since accumulation of serum iron was not observed, a dosing interval of 3-4 days (500 mg iron) or 1 week (1000 mg iron) was demonstrated to be adequate. The increase in serum ferritin and TSAT at the 4-week follow-up visit is indicative of a repletion of the iron stores. The results suggest that doses up to 1000 mg i.v. iron administered as FCM over 15 min arewell tolerated and effective in the treatment of patients with IDA due to a GI disorder.