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| Author(s): |
Kênnia Rocha Rezende
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2002-04-19 |
| Examining board members: |
Silvia Berlanga de Moraes Barros;
Luiz Carlos da Cunha;
Massuo Jorge Kato;
Jayme Antonio Aboin Sertie
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| Advisor: | Silvia Berlanga de Moraes Barros |
| Abstract | |
4-nerolidylcatechol (4-NRC) is the major constituent of a Piperaceae shrub, Pothomorphe umbellate (L.) Miq. Standardization of dry hydroalcoholic roots extract showed 21,5% of 4-NRC contents. The isolated compound was administrated intravenouslly or orally to rats Sprague Dawley at 10 mg/kg single dose. The crude extract was given at 100 mg/kg. Both pure compound and extract was dissolved in 30 % hydroxypropyl-β-cyclodextrin. The purpose of this work was to investigate the pharmacokinetic profile and the bioavailability of 4-NRC after oral administration. The assessement of plasma concentration was done with CLAE-EM/EM and the quantification limit was found to be 2.5 ng/mL. Linear response was done between 2.5-100 ng/mL and correlation coeficients were not lower than 0.98. Between batch and within-batch variation coeficient ranged from 2,9-10,1 and 4,2-16,3 %, respectively. Accuracy showed values between 84.4-92.4%. The pharmacokinetic parameters following intravenous and oral administration were calculated using Kinetica 2000 (Innaphase). Reported values for i.v. bollus volume of distribution was 0.47 L, and 6.08 min for elimination half-life (t½c). Area under the curve (AUC) was 187.06 µg/mL.min and total body clearance (CL) measured was 53.46 mL/min. The absortion peak plasma concentration (Cmax) was 34.90 ng/mL, reached after 23 min after oral dose administration. The calculated bioavailability for 4-NRC was 2,7%. Despite higher dose of 4-NRC in roots\' extract (21.5 mg/kg), its bioavailability was lower (1.1%). In fact, it was around one third of that one for pure compound. The data could be described with good fits indicating the drug is well distributed and highly metabolized. Plasma levels were found to be low as expected for lipophilic phenolic drug. (AU) | |