Effect of Carum carvi, a herbal bioenhancer on pharmacokinetics of antitubercular drugs: A study in healthy human volunteers

Abstract

Aim and Objectives:The present study was undertaken in 20 healthy human volunteers to evaluate the effect of a herbal bioenhancer, Carum carvi on pharmacokinetics of rifampicin, isoniazid, and pyrazinamide in fixed dose combination (FDC).Materials and Methods:It was a prospective, two-period, open-label, cross-over experiment on 20 healthy human male volunteers. The volunteers were administered a single dose of FDC containing rifampicin (450 mg), isoniazid (300 mg), and pyrazinamide (1000 mg) and after 10 days washout period the same FDC along with C. carvi extract (100 mg) was administered. Blood samples were collected at different time-points and analyzed by high-performance liquid chromatography (HPLC). Detailed pharmacokinetic parameters were calculated, which included Cmax, area under curve (AUC), time to reach maximum plasma concentration (Tmax), clearance (Cl), volume of distribution (Vd), and half-life (t½).Results:Additions of C. carvi extract lead to increase in plasma levels of rifampicin, isoniazid, and pyrazinamide. The bioavailability indices Cmax of rifampicin increased from 4.57 ± 0.19 to 5.95 ± 0.19 (P = 0.000) and AUC increased from 40.11 ± 1.69 to 53.01 ± 1.88 (P = 0.000). Similarly, Cmax of isoniazid increased from 2.66 ± 0.16 to 3.62 ± 0.16 (P = 0.000) and AUC from 17.72 ± 0.78 to 22.87 ± 0.94 (P = 0.000). The bioavailability indices of pyrazinamide also revealed an increase in Cmax from 18.81 ± 0.79 to 25.06 ± 1.14 (P = 0.000) and AUC from 107.65 ± 4.42 to 137.71 ± 5.92 (P = 0.000), respectively.Conclusion:C. carvi acts as a bioenhancer and modifies the kinetics of antitubercular treatment (ATT) favorably.

Matryoshka-Type Gastro-Resistant Microparticles for The Oral Treatment of Mycobacterium Tuberculosis

“…The plates were incubated overnight (37 °C in 5% CO 2 atmosphere). Non-loaded-PLGA NPs, rifampicin-loaded PLGA NPs or free rifampicin at minimum [19,20]and maximum [21][22][23]serum concentrations (4 and 24 µg/mL, respectively), were diluted in 200 µL of RPMI without phenol red per well and incubated for 24 h. The monolayers were washed once with DPBS and then 200 µL of fresh medium without phenol red and 20 µL of EZ4U were added. The absorbance was read after 4 h of incubation, and also at 48 h and 72 h. A microplate reader (Victor 3, Wallac) was used with a wavelength of 450 nm with 620 nm as reference.…”

“…Lastly, 1 mL of complete RPMI-1640 was added to each well and incubated for 72 h at 37 °C in a 5% CO 2 humidified incubator, in order to allow bacteria to grow inside the macrophages. After such incubation (day 0), fresh medium containing unloaded-PLGA NPs, rifampicin-loaded PLGA NPs or free rifampicin was added at 4 and 24 µg/mL (minimum [19,20]and maximum [21][22][23] serum concentrations). The quantity of rifampicin-loaded PLGA NPs added was calculated according to the rifampicin concentration inside the NPs.…”

Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism

“…The increase in C max was 32.22%, 36.01% and 33.22% for rifampicin, isoniazid and pyrazinamide, respectively, while the increase in AUC 0–24 h was 32.16%, 29.06% and 27.92% for rifampicin, isoniazid and pyrazinamide, respectively. According to the authors, the improvement in bioavailability caused by Caraway extract may be attributed to an enhancement of mucosal to serosal permeation as well as its influence on P-gp efflux [40]. Caraway was shown to act as an inhibitor of P-gp efflux and the main active components were found to be carvone and limonene [146].…”

Caraway as Important Medicinal Plants in Management of Diseases

“…Administration of 100 mg caraway with rifampin, isoniazid and pyrazinamide in 20 healthy volunteers increased the plasma levels of antibiotics. Caraway increased the bioavailability indices C max of antibiotics and area under curve (AUC) [ 68 ]. Caraway enhanced the action of rifampicin [ 69 ], isoniazid and pyrazinamide in rats [ 69 , 70 ].…”