Relationship between the venoconstrictor activity of dihydroergotamine and its pharmacokinetics during acute and chronic oral dosing.

In a double-blind, interindividual comparative study 30 healthy volunteers were randomly allocated to oral treatment with 5 or 10 mg of dihydroergotamine (DHE) or placebo once daily for 16 days. Regional basic venous blood volume (BBV), pressure dependent venous capacitance (CV) of the calf, resting heart rate and blood pressure were determined on Days 1 and 15 of treatment. Plasma concentrations of DHE were monitored on Days 2 and 16. Due to spontaneous vasodilation BBV varied considerably, showing that it is an inappropriate parameter for investigating the venoconstrictor activity of DHE. CV remained unchanged after the first dose of DHE but it had declined significantly on both dosage regimens at the end of the treatment phase. In contrast, the blood concentration profiles of DHE were comparable at the beginning and the end of the trial. The discrepancy can best be explained by the existence of an effect compartment, e.g. smooth vascular musculature, which slowly becomes filled with DHE and/or its active metabolites. The venoconstrictor activity of DHE exhibited a significant dose-response relationship.

[Error magnitude of measurement sensors in air segment plethysmography]. / Zur Fehlergrösse von Messfühlern bei der Luftsegmentplethysmographie.

Besides examining the properties of the material involved, this investigation assesses the so-called static and dynamic measurement errors of sensors used for air segment plethysmography. The static error which has been found with the new BN sensors amounts to 8% (old models: 31%-44%). The folding of the interior membrane of the sensor resting upon the skin, which increases proportionately to the stiffness of the material, is discussed as a source of error. If a lockable steel wrapping is employed as an exterior cover for the sensors, the static measurement error decreases by 30%-50%. These results suggest a recommendation to use a metal wrapping for the sensors as described above even with routine air segment plethysmographic examinations, and additionally to correct by mathematical means the static measurement error (which has to be determined for each sensor individually). The measurement error of the sensors of the new BN series amounts to less than 5% for a frequency of not more than 0.5 Hz; this means that blood flow values amounting to more than 50 ml/(min X 100 ml) are indicated correctly with respect to the actual frequency. If the usual linen covering is used instead of the steel cover, the linearity of the frequency is only valid up to 0.1 Hz--the corresponding blood flow value being 15 ml/(min X 100 ml).

[Evaluation of air segment plethysmography using computer tomography]. / Uberprüfung der Luftsegmentplethysmographie mittels Computertomographie.

The measurement of tissue volume in the calf area carried out by computer-tomography and planimetry showed a nearly elliptic form, an average bony part of 9.9 ml (9.3%), and an average tissue volume of 97.7 ml (90.7%). When compared with the tissue volume approximation (cylinder formula) the tissue volumes thus specified were too large. The error, depending on the circumference of the calf, was about 5 to 15%. There was a difference of 5% between the venous capacity measured by computer-tomography on the one hand and air segment plethysmography on the other. The reason for this is found in the varying density of veins in the examined area. The application of the sensor on the skin caused an average reduction of 5.4% in total volume and thus in the blood volume of about 59% in the examined area. The pressure-dependent venous capacity was measured with and without application of the sensors on the skin and controlled by computer-tomography. The results showed an average difference of only 2.1%. Thus it is obviously unimportant for the results of the investigation presented, if the venous capacity is measured on the basis of the reduced total volume caused by the application of the sensors on the skin. With regard to the computer-tomographical and planimetrical control and the error of measurement discussed, the results suggest a sufficient precision of the venoextensiometry measuring the pressure-dependent venous capacity.