Pharmacokinetics of the calcium-channel blocker diltiazem after a single intravenous dose in horses

The pharmacokinetics of diltiazem were determined in eight healthy horses. Diltiazem HCl, 1 mg/kg i.v., was administered over 5 min. Venous blood samples were collected at regular intervals after administration. Plasma concentrations of diltiazem and desacetyldiltiazem were determined by high-performance liquid chromatography. A second, putative metabolite was detected, but could not be identified due to the lack of an authentic standard. Data were analyzed by nonlinear least-squares regression analysis. The median (minimum-maximum) peak plasma concentration of diltiazem was 727 (539-976) ng/mL. Plasma diltiazem concentration vs. time data were best described by a two-compartment model with first-order drug elimination. The distribution half-life was 12 (6-23) min, the terminal half-life was 93 (73-161) min, the mean residence time was 125 (99-206) min, total plasma clearance was 14.4 (10.4-18.6) mL/kg/min, and the volume of distribution at steady-state was 1.84 (1.46-2.51) L/kg. The normalized ratio of the area under the curve (AUC) of desacetyldiltiazem to the AUC of diltiazem was 0.088 (0.062-0.179). The disposition of diltiazem in horses was characterized by rapid distribution and elimination and a terminal half-life shorter than reported in humans and dogs. Because of the reported low pharmacologic activity, plasma diltiazem metabolite concentrations were not considered clinically important

Hierarchy to homeostasis? Hierarchy, markets and networks in UK media and communications governance

The author considers propositions that market and network governance are supplanting hierarchical governance in contemporary UK media and communications, Liberalisation of media and communication markets, adoption of new public management in publicly owned bodies, “outsourcing” of regulation from statutory to self-regulatory bodies and “fourth way” co-ordination of Internet institutions suggest that the importance of markets and networks as potentially “homeostatic” modes of governance is growing. However, hierarchical governance remains important, the Communications Act 2003 prescribes more than 260 duties for the statutory regulator, Ofcom, and the BBC makes a major intervention in broadcasting markets. All three forms of governance fail in distinctive ways and the author argues both that the potential for network governance failure is less well recognised than are market and hierarchy failures and that the complexity of established governance arrangements itself constitutes a distinctive form of failure of governance