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Disposition of rifampicin following intranasal and oral administration
N V Mamidi1, M C Prabhakar, D R Krishna
1Drug Metabolism Laboratory, University College of Pharmaceutical Sciences, Kakatiya University, Waranga.
Abstract:
Leprosy is transmitted by dissemination of M.leprae which are lodged in the nose of the patients suffering from multibacillary (MB) type of the disease. Rifampicin, a potent bactericidal antileprotic drug is given orally to the patients with a view to make the infective cases non-infective. Earlier work by us has shown that intranasal administration of rifampicin helps in reducing the M.leprae load in the nose much faster than after conventional oral administration. In the present study, rifampicin concentrations in plasma/urine/nasal wash of healthy volunteers following oral and intranasal administration were determined. Following intranasal administration, rifampicin was not detectable in plasma and high concentrations were measured in the nasal wash. Following oral administration, rifampicin was not detectable in the nasal wash indicating that enough antibiotic levels are not available for clearing M.leprae from nose.
Insights
Intranasal administration of rifampicin effectively targets Mycobacterium leprae in the nose, unlike oral doses. This study shows direct nasal delivery achieves higher drug concentrations locally for faster bacterial clearance in leprosy patients.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Leprosy transmission involves Mycobacterium leprae (M.leprae) lodging in the nasal passages of multibacillary (MB) patients.
- Rifampicin is a key oral antibiotic used to render leprosy patients non-infective.
- Previous research suggests intranasal rifampicin may reduce nasal M.leprae load more rapidly than oral administration.
Purpose of the Study:
- To compare rifampicin concentrations in plasma, urine, and nasal wash after oral versus intranasal administration in healthy volunteers.
- To evaluate the local nasal drug availability for M.leprae clearance.
Main Methods:
- Healthy volunteers received either oral or intranasal rifampicin.
- Rifampicin levels were quantified in plasma, urine, and nasal wash samples.
Main Results:
- Intranasal administration resulted in undetectable plasma rifampicin but high nasal wash concentrations.
- Oral administration showed undetectable rifampicin in nasal wash, suggesting insufficient local antibiotic levels.
- Urine concentrations were not explicitly detailed but implied to be measurable.
Conclusions:
- Intranasal rifampicin delivery achieves high local concentrations in the nasal cavity, potentially enhancing M.leprae eradication.
- Conventional oral rifampicin may not provide adequate drug levels in the nose for effective M.leprae clearance.
- Direct intranasal drug delivery presents a promising strategy for treating nasal M.leprae colonization in leprosy.