Measurement of the bioavailability of aescin-containing extracts.

OBJECTIVE: In horse chestnut seed extracts (HCSE), the triterpene saponin mixture aescin is considered the active principle. The bioavailability and pharmacokinetics of different HCSE preparations have been studied under single and repeated applications using a radioimmunological method (RIA) developed to identify beta-aescin, one of the pharmacologically active fractions of the saponin mixture. In this paper, the available pharmacokinetic data are reviewed and the observed heterogenicity between comparable studies is discussed. DATA SOURCES: Pharmacokinetic data from 5 single- and 4 multiple-dose bioequivalence studies with HCSE-containing products, were measured by the same analytical laboratory using the same RIA. EVALUATION: In studies where procedures were identical the pharmacokinetic data of beta-aescin show high variations. Even under steady-state conditions a considerable variability for the same HCSE product is obtained. CONCLUSION: Formal reasons like study design and medications can be ruled out as a source of pharmacokinetic variation. In extracts of herbal drugs like HCS, the relative concentration of the individual saponin fractions can considerably differ from batch to batch. For immunological methods, identification of such antigens with intermolecular variability, e.g., the structural aescin analogs, is of unknown validity. Therefore the shape of the concentration-time curve would only show an approximation of the time course but not for the absolute concentrations. A specific validation procedure for the RIA must be developed, otherwise a LC-MS/MS-method of sufficient sensitivity should be elaborated.

[The validity of radioimmunologic determination of bioavailability of beta-escin in horse chestnut extracts]. / Zur Validität radioimmunologisch bestimmter Bioverfügbarkeitsdaten von beta-Aescin in Rosskastaniensamenextrakten.

The bioavailability under steady state conditions of a standard, slow-release horse chestnut seed extract (HCSE)-containing product was compared with that of an analogous, fast-release test preparation (Noricaven novo) in a prospective, randomised, double-blind study in a double cross-over design. The serum concentration of beta-escin (CAS 6805-41-0) was measured by radioimmunoassay. In addition, the biopharmaceutical properties of the HCSEs present in the products were investigated, the amount and composition of the active ingredient, escin, being analysed with a validated HPLC method. The pharmacokinetics of this study were compared with the corresponding data of a similar investigation carried out under analogous conditions concerning study design, analytical methods and reference preparation. Comparison of the similar studies revealed differences in characteristic pharmakokinetic values of beta-escin in terms of a shift of the concentration time curves as could be demonstrated for the reference product. The total amounts of escin in the two products investigated did not differ significantly. However, quantitative and qualitative differences were detected in the constituents of the two different extract preparations. It is concluded that the high specificity of the validated beta-escin radioimmunoassay leads to analytical imprecision due to the variable constituents of the extract preparations used. It is necessary to test whether this problem can be solved using an analytical approach, which is specific for each extract.

[Comparison of the bioavailability of beta-aescin after single oral administration of two different drug formulations containing an extract of horse-chestnut seeds]. / Vergleichende Untersuchung zur Bioverfügbarkeit von beta-Aescin nach oraler Einmalverabreichung zweier Rosskastaniensamenextrakt enthaltender, galenisch unterschiedlicher Darreichungsformen.

The relative oral bioavailability of beta-escine (CAS 11072-93-8) from a sugar-coated tablet formulation was compared to a reference preparation available in capsule form in 18 healthy, male volunteers over a 48 h period. The study design was randomized, single-blind and cross-over. Both the test and the reference preparation contained 50 mg standardized horse chestnut seed extract; beta-escine was taken as the reference substance. By means of a newly developed, validated radioimmunosorbent assay (RIA), beta-escine in plasma was determined (blind samples) after oral intake of a single dose of each drug formulation. The confidence limits calculated for the AUC, Cmax and Tmax of the test preparation exceed the upper limit of the specified equivalence range of 80%--125%, but do never fall below the lower limit. Therefore, bioin-equivalence cannot be rejected statistically. All the bioavailability data for the test preparation--measured with the newly developed RIA--exceed the corresponding values for the reference preparation. As the rate of absorption of aesculetinic triterpene glycosides is low, the higher bioavailability of the test preparation is desirable from a therapeutical point of view. Since the reference preparation is classified as being clinically effective, the test preparation must also be estimated as being clinically effective. Adverse drug effects were not observed with either the test preparation or the reference preparation.