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Rifampicin antagonizes the effect of choloroquine on chloroquine-resistant Plasmodium berghei in mice

Hou LJ, Raju SS, Abdulah MS, Nor NM, Ravichandran M

Jpn J Infect Dis, 2004 Oct;57(5):198-202.
PMID: 15507775

Chloroquine (CQ)-resistant Plasmodium falciparum appears to decrease CQ accumulation in its food vacuole by enhancing its efflux via an active membrane pump, which has been reported to be a P-glycoprotein-like transporter. Rifampicin (RIF) is a P-glycoprotein inhibitor and also has some antimalarial activity. It is hoped that a combination of choloroquine-rifampicin (CQ + RIF) would be advantageous in the treatment of CQ-resistant malaria. Swiss albino mice were inoculated with CQ-resistant P. berghei intraperitoneally, and studied for the effect of CQ versus the combination of CQ + RIF at various doses on the clearance of parasitemia, the survival of the mice, and the recrudescence of malaria. Paradoxically, RIF decreased the survival rate and rate of clearance of parasitemia and increased the rate of recrudescence significantly when combined with various doses of CQ. Our results indicated that RIF worsened the course of the disease, and we concluded that RIF should not be combined with CQ in the treatment of malaria.

Matched MeSH terms: Rifampin/administration & dosage
A bioequivalence comparison of two formulations of rifampicin (300- vs 150-mg capsules): An open-label, randomized, two-treatment, two-way crossover study in healthy volunteers

Chik Z, Basu RC, Pendek R, Lee TC, Mohamed Z

Clin Ther, 2010 Sep;32(10):1822-31.
PMID: 21194606 DOI: 10.1016/j.clinthera.2010.09.006

Rifampicin is a semisynthetic antibiotic derivative of rifamycin used worldwide for the treatment of various forms of tuberculosis.

Matched MeSH terms: Rifampin/administration & dosage*
Critical physicochemical and biological attributes of nanoemulsions for pulmonary delivery of rifampicin by nebulization technique in tuberculosis treatment

Shah K, Chan LW, Wong TW

Drug Deliv, 2017 Nov;24(1):1631-1647.
PMID: 29063794 DOI: 10.1080/10717544.2017.1384298

The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.

Matched MeSH terms: Rifampin/administration & dosage*
Ocular leprosy in West Malaysia. Search for a posterior segment lesion

Weerekoon L

Br J Ophthalmol, 1972 Feb;56(2):106-13.
PMID: 5010311
Matched MeSH terms: Rifampin/administration & dosage
Inhalation of Respirable Crystalline Rifapentine Particles Induces Pulmonary Inflammation

Parumasivam T, Ashhurst AS, Nagalingam G, Britton WJ, Chan HK

Mol Pharm, 2017 01 03;14(1):328-335.
PMID: 27977216 DOI: 10.1021/acs.molpharmaceut.6b00905

Rifapentine is an anti-tuberculosis (anti-TB) drug with a prolonged half-life, but oral delivery results in low concentrations in the lungs because of its high binding (98%) to plasma proteins. We have shown that inhalation of crystalline rifapentine overcomes the limitations of oral delivery by significantly enhancing and prolonging the drug concentration in the lungs. The delivery of crystalline particles to the lungs may promote inflammation. This in vivo study characterizes the inflammatory response caused by pulmonary deposition of the rifapentine particles. The rifapentine powder was delivered to BALB/c mice by intratracheal insufflation at a dose of 20 mg/kg. The inflammatory response in the lungs and bronchoalveolar lavage (BAL) was examined at 12 h, 24 h, and 7 days post-treatment by flow cytometry and histopathology. At 12 and 24 h post-treatment, there was a significant influx of neutrophils into the lungs, and this returned to normal by day 7. A significant recruitment of macrophages occurred in the BAL at 24 h. Consistent with these findings, histopathological analysis demonstrated pulmonary vascular congestion and significant macrophage recruitment at 12 and 24 h post-treatment. In conclusion, the pulmonary delivery of crystalline rifapentine caused a transient neutrophil-associated inflammatory response in the lungs that resolved over 7 days. This observation may limit pulmonary delivery of rifapentine to once a week at a dose of 20 mg/kg or less. The effectiveness of weekly dosing with inhalable rifapentine will be assessed in murine Mycobacterium tuberculosis infection.

Matched MeSH terms: Rifampin/administration & dosage
Comparative Efficacy of Antimicrobial Central Venous Catheters in Reducing Catheter-Related Bloodstream Infections in Adults: Abridged Cochrane Systematic Review and Network Meta-Analysis

Chong HY, Lai NM, Apisarnthanarak A, Chaiyakunapruk N

Clin Infect Dis, 2017 May 15;64(suppl_2):S131-S140.
PMID: 28475779 DOI: 10.1093/cid/cix019

Background: The efficacy of antimicrobial central venous catheters (CVCs) remains questionable. In this network meta-analysis, we aimed to assess the comparative efficacy of antimicrobial CVC impregnations in reducing catheter-related infections in adults.
Methods: We searched 4 electronic databases (Medline, the Cochrane Central Register of Controlled Trials, Embase, CINAHL) and internet sources for randomized controlled trials, ongoing clinical trials, and unpublished studies up to August 2016. Studies that assessed CVCs with antimicrobial impregnation with nonimpregnated catheters or catheters with another impregnation were included. Primary outcomes were clinically diagnosed sepsis, catheter-related bloodstream infection (CRBSI), and all-cause mortality. We performed a network meta-analysis to estimate risk ratio (RR) with 95% confidence interval (CI).
Results: Sixty studies with 17255 catheters were included. The effects of 14 impregnations were investigated. Both CRBSI and catheter colonization were the most commonly evaluated outcomes. Silver-impregnated CVCs significantly reduced clinically diagnosed sepsis compared with silver-impregnated cuffs (RR, 0.54 [95% CI, .29-.99]). When compared to no impregnation, significant CRBSI reduction was associated with minocycline-rifampicin (RR, 0.29 [95% CI, .16-.52]) and silver (RR, 0.57 [95% CI, .38-.86]) impregnations. No impregnations significantly reduced all-cause mortality. For catheter colonization, significant decreases were shown by miconazole-rifampicin (RR, 0.14 [95% CI, .05-.36]), 5-fluorouracil (RR, 0.34 [95% CI, .14-.82]), and chlorhexidine-silver sulfadiazine (RR, 0.60 [95% CI, .50-.72]) impregnations compared with no impregnation. None of the studies evaluated antibiotic/antiseptic resistance as the outcome.
Conclusions: Current evidence suggests that the minocycline-rifampicin-impregnated CVC appears to be the most effective in preventing CRBSI. However, its overall benefits in reducing clinical sepsis and mortality remain uncertain. Surveillance for antibiotic resistance attributed to the routine use of antimicrobial-impregnated CVCs should be emphasized in future trials.

Matched MeSH terms: Rifampin/administration & dosage