Pharmacokinetics of the antidepressant levoprotiline after intravenous and peroral administration in healthy volunteers.

To investigate the pharmacokinetics and the disposition of levoprotiline after i.v. and p.o. administration and to assess the absolute bioavailability, 12 healthy volunteers (11 women, 1 man) were given a 10 min i.v. infusion of 15 mg and a p.o. dose of 75 mg in a two-way crossover study. Blood and urine samples were collected after each dose. Unchanged levoprotiline and the sum of unchanged and glucuronidated levoprotiline (= total levoprotiline) were determined by a specific gas chromatographic-mass spectro-metric method. Intravenous levoprotiline was rapidly and extensively distributed into extravascular sites of the body; the steady-state volume of distribution was 18.81 kg-1. The elimination of levoprotiline from blood was independent of the dosing route, the half-life being 18.8 h. Only 1.8 and 0.6 per cent of the i.v. and p.o. dose, respectively, were excreted unchanged in the urine, whereas 57 per cent of each dose were renally excreted as total levoprotiline. The absolute bioavailability of p.o. levoprotiline was 40 per cent. About 60 per cent of the dose was subject to a first-pass effect in the liver. The systemic blood clearance of levoprotiline, determined after i.v. dosing, was 885 ml min-1, the renal blood clearance after i.v. and p.o. dosing was only 16.0 and 14.2 ml min-1, respectively. Presystemic and systemic clearance of levoprotiline occurred predominantly by direct glucuronidation

Radiographic reconstruction of lower-extremity bone fragments: a first trial.

PURPOSE The correct rotational alignment of the proximal and the distal bone fragments is an essential step in a long-bone deformity correction process. In order to plan the deformity correction, plain radiographs are conventionally used. But as three-dimensional information of the complex situation is not available, the correct amount of rotation can only be approximated. Thus, the objective of this study was to develop a system to assess the rotational relationship between the proximal and distal fragments of a long bone (tibia or femur) based on a set of two calibrated X-ray radiographs. METHODS In order to robustly determine the rotational relationship of proximal and distal bone fragments, a statistical shape model-based 2D/3D reconstruction approach was employed. The resulting fragment models were used to determine the angle between its anatomical axes and the rotation around its particular axes. Two different studies were performed to evaluate the accuracy of the proposed system. RESULTS The accuracy of the complete system was evaluated in terms of major bone axis and in-plane rotational difference. The angle between the anatomical fragment axes could be measured with an average error of 0.33[Formula: see text] ± 0.27[Formula: see text], while an average in-plane rotational error of 2.27[Formula: see text] ± 1.76[Formula: see text]  and 2.67[Formula: see text]  ± 1.80[Formula: see text]  was found for the proximal and distal fragments, respectively. The overall mean surface reconstruction error was 0.81  ± 0.59 mm when the present technique was applied to the tibia and 1.12 ± 0.87 mm when it was applied to the femur. CONCLUSIONS A new approach for estimating the rotational parameters of long-bone fragments has been proposed. This approach is based on two conventional radiographs and 2D/3D reconstruction technology. It is generally applicable to the alignment of any long-bone fragments and could provide an important means for achieving accurate rotational alignment