Effect of pH, mucin and bovine serum on rifampicin permeability through Caco‐2 cells

Abstract

Rifampicin, a poorly soluble drug, has great importance in therapeutics as it is the main drug used to treat tuberculosis. The characterization of its permeability and the factors that influence it represent an important tool for predicting its bioavailability. Caco-2 cell monolayers were used as models of the intestinal mucosa to assess the uptake and transport of rifampicin and the effects of various experimental conditions were investigated, in order to establish the influence of these variables on rifampicin permeability. Different pHs (5.8, 6.8 and 7.4) in the apical medium, the presence or absence of mucin (3.0% w/v) in the donor site and the presence or absence of bovine serum albumin (4.0% v/v) in the receptor chamber were the evaluated conditions. The quantification of rifampicin in the apical or basolateral chambers was performed by a validated HPLC-UV method. The change in the donor chamber pH showed that permeability values were greater at pH 6.8, although this increase does not result in an alteration of the qualitative classification of rifampicin, which has high permeability. Mucin and bovine serum showed no effects on the permeability of rifampicin at the concentration tested. Overall, the current study suggests that pH, artificial mucin and bovine serum proteins have no influence on rifampicin permeability.

Human topoisomerase inhibition and DNA/BSA binding of Ru(II)–SCAR complexes as potential anticancer candidates for oral application

“…The mean of the P app values obtained for fluorescein and verapamil was 0.11 9 10 -6 and 41.08 9 10 -6 cm s -1 , respectively. These values are in agreement with those obtained in the literature, indicating the adequacy of the cultivation conditions of Caco-2 cells as well as the reliability of the results obtained for the complexes (Gonçalves et al 2012;Chang et al 2013).…”

Development of a Multicompartment Permeability‐Limited Lung PBPK Model and Its Application in Predicting Pulmonary Pharmacokinetics of Antituberculosis Drugs

“…The unionized fraction of rifampicin at pH 7.4 is 4.7 × 10 −7 and that of clarithromycin is 0.025. For isoniazid, no permeability data in Calu‐3 cell monolayers were found in the literature, so permeability was estimated using the correlation with Caco‐2 data . Isoniazid is essentially unionized at pH 7.4 (fni = 0.999).…”

“…For isoniazid, no permeability data in Calu-3 cell monolayers were found in the literature, so permeability was estimated using the correlation with Caco-2 data. 35,36 Isoniazid is essentially unionized at pH 7.4 (fni 5 0.999). Performance verification for ethambutol, pyrazinamide, and isoniazid compound files The ability of the developed models to recover plasma concentrations of ethambutol, pyrazinamide, and isoniazid were checked by comparing predicted plasma concentrations with published data using similar study designs and subject demographics ( Supplementary Table 1).…”

Intestinal absorption of S-nitrosothiols: Permeability and transport mechanisms

“…So, the S-nitrosothiols included in the medium class of permeability can be considered as drugs suitable for oral administration. Thereafter, it would be interesting to study the permeability of S-nitrosothiols in the presence of albumin in the basolateral compartment to mimic the blood stream compartment [50]. Furthermore, albumin including a free reduced cysteine residue in position 34 will increase the amount of RSNO found in the basolateral compartment through S-nitrosation process.…”