Hayden JC, Bardol M, Doherty DR, et al. - In order to assess the adequacy of clonidine dosage regimens employed in clinical practice and research investigations, researchers intended to suggest a target plasma concentration and simulate clonidine pharmacokinetics in a cohort of mechanically ventilated children. Via a literature search, they identified a clonidine pharmaockinetic-pharmacodynamics model, from which, they defined a target concentration for sedation. They proposed a target plasma concentration of above 2 µg/L. Assessment of 9 dosage regimens (4 intravenous boluses, 4 intravenous infusions, and 1 nasogastric route boluses) was done, ranging from 1 µg/kg eight hourly intravenous boluses to a regimen up to 3 µg/kg/hr continuous intravenous infusion. Most suitable regimens were those with a loading dose of 2 µg/kg followed by variable continuous infusion of up to 2 µg/kg/hr titrated according to sedation score. In neonates, halving the doses was recommended. In order to achieve adequate steady-state concentrations of clonidine early in treatment, the necessity of a loading dose followed by higher than current practice maintenance dose infusion was indicated by simulations of clonidine plasma levels based on established population pharmacokinetic parameters.