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To cite this article: Grove EL, Hvas AM, Mortensen SB, Larsen SB, Kristensen SD. Effect of platelet turnover on whole blood platelet aggregation in patients with coronary artery disease. J Thromb Haemost 2011; 9: 185-91. Summary.Background: Previous studies have demonstrated considerable variation in the antiplatelet effect of aspirin. Objectives: To investigate the impact of platelet turnover on the antiplatelet effect of aspirin in patients with stable coronary artery disease (CAD) and to identify determinants of platelet turnover. Methods: Platelet turnover was evaluated by measurements of immature platelets and thrombopoietin in 177 stable CAD patients on aspirin monotherapy, including 85 type 2 diabetics and 92 non-diabetics. Whole blood platelet aggregation was determined using the VerifyNow Ò Aspirin test and multiple electrode aggregometry (MEA, Multiplate , P = 0.034). In a multivariate regression analysis, immature platelet levels were determined by thrombopoietin levels (P < 0.001), smoking (P = 0.020) and type 2 diabetes (P = 0.042). Conclusions: The antiplatelet effect of aspirin was reduced in CAD patients with an increased platelet turnover. Once-daily dosing of aspirin might not suffice to adequately inhibit platelet aggregation in patients with an increased platelet turnover.

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This review article provides an assessment of advantages/limitations of the use of current in vitro release models to predict in vivo performance of parenteral sustained release products (injectable depots). As highlighted, key characteristics influencing the in vivo drug fate may vary with the route of administration and the type of sustained release formulation. To this end, an account is given on three representative injection sites (intramuscular, subcutaneous and intra-articular) as well as on in vitro release mechanism(s) of drugs from five commonly investigated depot principles (suspensions, microspheres, hydrogels, lipophilic solutions, and liposomes/other nano-size formulations). Current in vitro release models are, to a different extent, able to mimic the rate, transport and equilibrium processes that the drug substance may experience in the environment of the administration site. Their utility for the purpose of quality control including in vitro-in vivo correlations and formulation design is discussed.

Visualization as well as quantification of nicotine concentration gradients was achieved by UV imaging in real time. UV imaging has the potential to become an important technology platform for conducting in vitro drug release studies.

This report details the structural characterization and the in vitro drug-release properties of different local anesthetic bupivacaine (BUP)-loaded inverted-type liquid crystalline phases and microemulsions. The effects of variations in the lipid composition and/or BUP concentration on the self-assembled nanostructures were investigated in the presence of the commercial distilled glycerol monooleate Myverol 18-99K (GMO) and medium-chain triglycerides (MCT). Synchrotron small-angle X-ray scattering (SAXS) and rotating dialysis cell model were used to characterize the BUP formulations and to investigate the in vitro BUP release profiles, respectively. The evaluation of SAXS data for the BUP-loaded GMO/MCT formulations indicates the structural transition of inverted-type bicontinuous cubic phase of the symmetry Pn3m → inverted-type hexagonal (H(2)) phase → inverted-type microemulsion (L(2)) with increasing MCT content (0-40 wt %). In the absence of MCT, the solubilization of BUP induces the transition of Pn3m → H(2) at pH 7.4; whereas a transition of Pn3m → (Pn3m + H(2)) is detected as the hydration is achieved at pH 6.0. To mimic the drug release and transport from in situ formed self-assembled systems after subcutaneous administration, the release experiments were performed by injecting low viscous stimulus-responsive precursors to a buffer in the dialysis cell leaving the surface area between the self-assembled system and the release medium variable. Our results suggest that the pH-dependent variations in the lipidic partition coefficient, K(l/w), between the liquid crystalline nanostructures and the surrounding buffer solution are significantly affecting BUP release rates. Thus, a first step toward understanding of the drug-release mechanism of this drug-delivery class has been undertaken tackling the influence of drug ionization as well as the type of the self-assembled nanostructure and its release kinetics under pharmaceutically relevant conditions.

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