ABSTRACT
This study deals with the pharmacokinetic interaction of selected anti-TB drugs with a natural product (CC-1a) derived from caraway (Carum carvi, L.) seed. CC-1a, chemically standardized butanolic fraction, enhanced the plasma levels of rifampicin, pyrazinamide, and isoniazid in Wistar rat, resulting in increased bioavailability indices (C(max) and AUC) of the drugs. Moreover, a 40% reduced dose regimen of these drugs, which additionally contained CC-1a, was equivalent in terms of C(max) and AUC to a normal dose regimen. A permeation-enhancing property of CC-1a across small intestinal absorptive surface was found to be a contributing factor in its bioavailability enhancing profile.
Subject(s)
Antitubercular Agents/pharmacokinetics , Carum/chemistry , Animals , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Drug Interactions , Female , Intestinal Absorption/drug effects , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Isoniazid/pharmacokinetics , Jejunum/metabolism , Male , Plant Extracts/pharmacology , Pyrazinamide/pharmacokinetics , Rats , Rats, Wistar , Reference Standards , Rifampin/pharmacokinetics , Seeds/chemistry , SolventsABSTRACT
A specific and sensitive high-performance liquid chromatographic (HPLC) method with photodiode-array (PDA) ultraviolet detection was developed for the simultaneous determination of three bioactive constituents of Cedrus deodara namely wikstromol, matairesinol and dibenzylbutyrolactol in mouse plasma. In solid-phase extraction (SPE) these constituents were successfully separated using a C18 column by isocratic elution using acetonitrile:water containing hexanesulphonic acid, 32:68 (v/v). The flow rate was set at 1ml/min and detector wavelength at 225nm. Good linearity (r2>0.999) was observed over the studied range of 0.015-5.0microg/ml for wikstromol and 0.030-5.0microg/ml for matairesinol and dibenzylbutyrolactol. The CV values of intra-day precision for wikstromol, matairesinol and dibenzylbutyrolactol were in between 1.8-6.9, 1.7-4.9 and 1.6-4.2% and values of inter-day precision were in between 10.4-12.2, 9.7-11 and 10-11.2%, respectively. The extraction recoveries at low to high concentration were greater than 98, 83 and 87% for each analyte, respectively. The LOQ for wikstromol was 0.015microg/ml and for both matairesinol and dibenzylbutyrolactol it was 0.030microg/ml. The developed method was used to determine the pharmacokinetics of the three analytes in mice after intraperitoneal administration of CD-3.
Subject(s)
Cedrus/chemistry , Chromatography, High Pressure Liquid/methods , Plant Extracts/chemistry , Plant Extracts/pharmacokinetics , Animals , Mice , Reference Standards , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The bioavailability of rifampicin (RIF) in a fixed dose combination (FDC) used for the treatment of tuberculosis remains an area of clinical concern and several pharmaceutical alternatives are being explored to overcome this problem. The present study presents a pharmacological approach in which the bioavailability of a drug may be modulated by utilizing the herb-drug synergism. The pharmacokinetic interaction of some herbal products and a pure molecule isolated from Cuminum cyminum with RIF is shown in this paper. An aqueous extract derived from cumin seeds produced a significant enhancement of RIF levels in rat plasma. This activity was found to be due to a flavonoid glycoside, 3',5-dihydroxyflavone 7-O-beta-D-galacturonide 4'-O-beta-D-glucopyranoside (CC-I). CC-I enhanced the Cmax by 35% and AUC by 53% of RIF. The altered bioavailability profile of RIF could be attributed to a permeation enhancing effect of this glycoside.
