Prasugrel (CAS 150322-43-3), an inhibitor of platelet activation and aggregation, is indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome. If a proton pump inhibitor is co-administered with prasugrel, a pH dependent salt-to-base conversion rate of prasugrel could become clinically meaningful. In an open-label, randomized, four-period, 2 x two-way crossover study, the relative bioavailability of tablets containing prasugrel free base compared to prasugrel hydrochloride (originator product) both in the presence and in the absence of the proton pump inhibitor lansoprazole (CAS 103577-45-3) was investigated. In the absence of lansoprazole, the extent of absorption (AUC) of prasugrel free base was about 8-9% lower, while the rate of absorption (Cmax) after administration of prasugrel free base was 20% lower when compared to prasugrel hydrochloride. When lansoprazole was used to raise the pH level in the upper gastro-intestinal tract, AUC was decreased by 25% after administration of prasugrel hydrochloride and by 41% after prasugrel free base. In addition, the peak plasma levels were decreased by 52% and 72%, respectively (geometric means). The relative bioavailability of the prasugrel free base compared to prasugrel hydrochloride, both in the presence and in the absence of the proton pump inhibitor lansoprazole, differs so much that most probably a generic formulation containing prasugrel free base will not be equivalent in all aspects to the originator product.

The bioavailability of two exemestane tablet formulations was compared in 74 healthy post-menopausal females, aged 46 to 74 years, during a laboratory-blind, randomized, two-treatment, two-period, cross-over study under fed conditions. In each treatment phase subjects received a single dose (one tablet) of 25 mg exemestane (CAS 107868-30-4). Consecutive dosing was separated by a drug-free washout period of 21 d. Following each dosing, serial venous blood samples were collected over a period of 144 h for the determination of plasma exemestane concentrations by means of a validated LC-MS/MS method. The geometric mean Cmax of exemestane for the reference and test products was 21.48 and 20.14 ng/mL, respectively. The corresponding mean AUC(0-infinity) was 87.12 and 86.90 ng x h/mL. The median Tmax for both products under investigation appeared at 1.70 and 1.97 h, respectively. The test product was well tolerated and shown to be bioequivalent to the reference product with respect to all primary pharmacokinetic variables investigated.

Repeated anorectal administration of a 5% lidocaine ointment proved to be safe with respect to systemic plasma concentrations of lidocaine and vital signs.

AimsTransdermal fentanyl is a well established treatment for cancer pain. The aim of the present study is to assess the relative bioavailability of fentanyl from two different transdermal systems by evaluating plasma drug concentrations after single administration of Fentalgon® (test), a novel bilayer matrix type patch, and Durogesic SMAT (reference), a monolayer matrix type patch. In the Fentalgon patch the upper 6% fentanyl reservoir layer maintains a stable concentration gradient between the lower 4% donor layer and the skin. The system provides a constant drug delivery over 72 h.MethodsThis was an open label, single centre, randomized, single dose, two period crossover clinical trial, that included 36 healthy male volunteers. The patches were applied to non-irritated and non-irradiated skin on the intraclavicular pectoral area. Blood samples were collected at different time points (from baseline to 120 h post-removal of the devices) and fentanyl concentrations were determined using a validated LC/MS/MS method. Bioequivalence was to be claimed if the 90% confidence interval of AUC(0,t) and Cmax ratios (test: reference) were within the acceptance range of 80–125% and 75–133%, respectively.ResultsThe 90% confidence intervals of the AUC(0,t) ratio (116.3% [109.6, 123.4%]) and Cmax ratio (114.4% [105.8, 123.8%] were well included in the acceptance range and the Cmax ratio also met the narrower bounds of 80–125%. There was no relevant difference in overall safety profiles of the two preparations investigated, which were adequately tolerated, as expected for opioid-naïve subjects.ConclusionsThe new bilayer matrix type patch, Fentalgon®, is bioequivalent to the monolayer matrix type Durogesic SMAT fentanyl patch with respect to the rate and extent of exposure of fentanyl (Eudra/CT no. 2005-000046-36).