Pharmacokinetic Comparison Between a Fixed-Dose Combination of Atorvastatin/Omega-3-Acid Ethyl Esters and the Corresponding Loose Combination in Healthy Korean Male Subjects.

Purpose: Statins are widely used in combination with omega-3 fatty acids for the treatment of patients with dyslipidemia. The aim of this study was to compare the pharmacokinetic (PK) profiles of atorvastatin and omega-3-acid ethyl esters between fixed-dose combination (FDC) and loose combination in healthy subjects. Methods: A randomized, open-label, single-dose, 2-sequence, 2-treatment, 4-period replicated crossover study was performed. Subjects were randomly assigned to one of the 2 sequences and alternately received four FDC soft capsules of atorvastatin/omega-3-acid ethyl esters (10/1000 mg) or a loose combination of atorvastatin tablets (10 mg × 4) and omega-3-acid ethyl ester soft capsules (1000 mg× 4) for four periods, each period accompanied by a high-fat meal. Serial blood samples were collected for PK analysis of atorvastatin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). PK parameters were calculated by a non-compartmental analysis. The geometric mean ratio (GMR) and its 90% confidence interval (CI) of the FDC to the loose combination were calculated to compare PK parameters. Results: A total of 43 subjects completed the study as planned. The GMR (90% CI) of FDC to loose combination for maximum concentration (Cmax) and area under the time-concentration curve from zero to the last measurable point (AUClast) were 1.0931 (1.0054-1.1883) and 0.9885 (0.9588-1.0192) for atorvastatin, 0.9607 (0.9068-1.0178) and 0.9770 (0.9239-1.0331) for EPA, and 0.9961 (0.9127-1.0871) and 0.9634 (0.8830-1.0512) for DHA, respectively. The intra-subject variability for Cmax and AUClast of DHA was 30.8% and 37.5%, respectively, showing high variability. Both the FDC and the loose combination were safe and well tolerated. Conclusion: The FDC of atorvastatin and omega-3-acid ethyl esters showed comparable PK characteristics to the corresponding loose combination, offering a convenient therapeutic option for the treatment of dyslipidemia.

Comparative Pharmacodynamics Study of 3 Different Botulinum Toxin Type A Preparations in Mice.

BACKGROUND: A new complexing protein-free botulinum toxin Type A (CBoNT) with the same mechanism of action as the botulinum toxin complex onabotulinumtoxinA (OBoNT) and complexing protein-free incobotulinumtoxinA (IBoNT) was recently developed. OBJECTIVE: To compare the local paresis and chemodenervation efficacy of 3 different botulinum toxin Type A preparations in mice. MATERIALS AND METHODS: Efficacy and duration of action of CBoNT, OBoNT, and IBoNT after a single intramuscular injection to the right gastrocnemius was evaluated by digit abduction score (DAS) and compound muscle action potential (CMAP) assays. RESULTS: Mouse DAS and CMAP responses were comparable between CBoNT and OBoNT, indicating similar paresis and chemodenervation efficacy, as well as duration of action. Both botulinum toxins showed significantly higher efficacy and longer duration of action than IBoNT. Similarly, mean DAS potency of CBoNT (ED50: 3.85 ± 0.34 U/kg) and OBoNT (ED50: 4.13 ± 0.07 U/kg) were significantly higher compared with IBoNT (ED50: 6.70 ± 0.83 U/kg). CONCLUSION: CBoNT displays the same efficacy as OBoNT as shown by their comparable chemodenervation and local paretic effects, and demonstrates superior efficacy and duration of action compared with IBoNT. Likewise, CBoNT has comparable DAS potency to OBoNT and is superior to IBoNT.