Europ. J. clin. Pharmacol. 11,435-438 (1977)

European Journal of Clinical Pharmacology @ by Springer-Verlag 1977

The Effect of Hydroxyethylrutosides on Capillary Filtration Rate in the Lower Limb of Man K. Roztoril, I. P~erovsk3~, and I. Oliva Clinical Pharmacology Research Centre of the Institute for Clinical and Experimental Medicine, Praha, Czechoslovakia

Summary. The rate of capillary filtration in the lower limbs after hydroxyethylrutosides administered in various doses and by different routes was studied in patients with chronic venous insufficiency. Capillary filtration rate decreased immediately after intravenous and from 55 to 85 minutes after oral administration, depending on the dose. The slow-release tablets produced a definite falt in capillary filtration 240 minutes after administration. Key words: Hydroxyethylrutosides, capillary filtration rate, venous insufficiency, plethysmography.

After a single intravenous dose of hydroxyethylrutosides in patients with chronic venous insufficiency a significant decrease of capillary filtration rate was found, whereas blood flow and venous capacity remained unchanged (Roztoril et al., 1971). An identical effect was observed after oral administration of the drug (P~erovsk~ et al., 1973). The present study was undertaken to ascertain the dynamics of the observed changes in capillary filtration, to compare the effects of different doses and routes of administration, and to evaluate the effect of slowrelease tablets.

Material and Methods Patients were examined in the supine position, at a room temperature of 21-23°C. Prior to measurement, the patients lay flat and at rest for 30 min. To determine the capillary filtration rate, the method of venous occlusion plethysmography (occlusion pressure 60 mm Hg) was used. Volume changes

were measured by a mercury-in-rubber strain-gauge plethysmograph (Whitney, 1953). Occlusion cuffs were placed above the knee and venous occlusion was applied for 5 min. In accordance with other studies (Krogh et al., 1932; Landis and Gibbon, 1933; Mellander and Oberg, 1967) distal arterial occlusion was not used during the measurements. From the tangent drawn to the plethysmographic curve during the 3rd to 5th minutes of occlusion, capillary filtration rate, expressed in ml/100 ml per minute was determined (Kitchin, 1963). After assessment of the initial values, the capillary filtration rate was determined at 10min intervals up to 120 min after drug administration. Hydroxyethylrutosides were given as follows: intravenously 1 ampoule (500 mg), orally 1 capsule (300 mg) or 3 capsules (900 mg). Because of the results of previous double-blind trials (Rozto~il et al., 1971; P~erovsk~) et al., 1973) no control measurements with placebo were used in the present experiments. In all 40 limbs in 21 patients with chronic venous insufficiency, were tested age range 34-72, 7 males and 14 females. The causal factor in 9 patients was primary varices, in 7 a post-thrombotic syndrome, and in 5 a combination of primary varices with a post.-thrombotic syndrome. A further series of measurements was done to evaluate the effect of a slow-release preparation of hydroxyethylrutosides (Venoruton-Retard ® The capillary filtration values before and 120 and 240 min after oral administration of 1 tablet containing 300 mg of active substance were compared. Control measurements were made using 1 tablet of placebo. In a double-blind cross-over trial, altogether 40 examinations were done of 22 limbs in 11 patients with chronic venous insufficiency; 3 males and 8 females, aged 33 to 67 years. Causal factors were primary varices in 7 patients, a post-

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K. Rozto6il et al.: Hydroxyethylrutosides and Capillary Filtration

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thrombotic syndrome in 2 and in the remaining 2 a combination of varices and a post-thrombotic syndrome. The diagnoses were established by clinical investigation and the history. The manifestations of chronic venous insufficiency (Kappert, 1974) were present in 41 extremities: oedema in 36, hyperpigmentations in 21, induration in 14 and ulcers in 3 cases. The results were analysed statistically using the paired Student's t-test (Fisher, 1946).

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Results

The mean values of capillary filtration rate and its changes after intravenous and oral administration of hydroxyethylrutosides are shown in Figure 1. Injection produced an immediate decrease in capillary filtration rate, as compared with an average delay of 85rain after oral administration of 1 capsule (300 mg; see Tables 1 and 2). Measured 120 min after the injection, the capillary filtration rate had returned to its initial level, whereas after 1 capsule it remained reduced. The mean values of capillary filtration rate after 300 and 900 mg (1 and 3 capsules, respectively) of hydroxyethylrutosides are compared in Figure 2. On average, significantly lower values were found 55 min after 3 capsules (Table 3). The decrease in capillary filtration rate reached its lowest level after the 120 minute of measurement, and there was no tendency for it to return to the initial value. The decrease after 1 and 3 capsules averaged at the most 32 and 50% of the initial values, respectively. The difference between the effect of the two doses was statistically significant (p