Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 2784  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Article Submission Resources Sections Etcetera Contact
 
  NAVIGATE Here 
  Search
 
 :: Next article
 :: Previous article 
 :: Table of Contents
  
 RESOURCE Links
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::  Article in PDF (37 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Acknowledgment
 ::  References
 ::  Article Tables

 Article Access Statistics
    Viewed3240    
    Printed73    
    Emailed0    
    PDF Downloaded115    
    Comments [Add]    
    Cited by others 7    

Recommend this journal


 


 
LETTER
Year : 2008  |  Volume : 54  |  Issue : 3  |  Page : 245-246

Low-dose inhaled versus standard dose oral form of anti-tubercular drugs: Concentrations in bronchial epithelial lining fluid, alveolar macrophage and serum


Department of Tuberculosis and Respiratory Diseases, Dr. ML Chest Hospital, GSVM Medical College, Kanpur, India

Correspondence Address:
S Prakash
Department of Tuberculosis and Respiratory Diseases, Dr. ML Chest Hospital, GSVM Medical College, Kanpur
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0022-3859.41823

Rights and Permissions




How to cite this article:
Katiyar S K, Bihari S, Prakash S. Low-dose inhaled versus standard dose oral form of anti-tubercular drugs: Concentrations in bronchial epithelial lining fluid, alveolar macrophage and serum. J Postgrad Med 2008;54:245-6

How to cite this URL:
Katiyar S K, Bihari S, Prakash S. Low-dose inhaled versus standard dose oral form of anti-tubercular drugs: Concentrations in bronchial epithelial lining fluid, alveolar macrophage and serum. J Postgrad Med [serial online] 2008 [cited 2019 Nov 17];54:245-6. Available from: http://www.jpgmonline.com/text.asp?2008/54/3/245/41823


Sir,

Patients with pulmonary tuberculosis could benefit from the use of inhaled anti-tubercular drug (ATD) administration as it would deliver the drug directly at the site of infection. [1] It is also likely that lower doses would be required when the drugs are administered by inhalation. [2]

A 'proof of concept' study was undertaken for comparing the concentrations of rifampicin (RIF), isoniazid (INH) and pyrazinamide (Z) in the epithelial lining fluid (ELF), alveolar macrophages (AM) and serum following low-dose administration via inhaled route and those following standard dose administration via oral route.

Following the approval of the Institutional Ethics Committee, healthy volunteers aged 20-50 years without prior history of tuberculosis and with baseline forced expiratory volume at 1 sec (FEV1) over 60% of predicted value for height, weight and gender were enrolled.

Informed consent was obtained prior to enrollment. The subjects were then randomized into two groups: Six subjects in Group A received capsule containing micro-particles of anti-tubercular drugs (ATD, INH 15 mg, RIF 30 mg and Z 75 mg with lactose as a carrier particle) using a dry powder inhaler. The particle size ranged from 1-10 with mass median aerodynamic diameter of 2.79 . The remaining six subjects in Group B received oral ATD (a tablet containing RIF 500 mg, INH 250 mg and Z 1250 mg) as a single dose at 8 h of fasting. As shown in [Table 1] the mean concentrations of INH, Z and RIF achieved in ELF were 220, 15 and 83 times higher in the inhaled group than those in the oral ATD group. Similarly, the median AM intracellular concentrations of INH, Z and RIF in inhaled group were 96, 29 and 113 times higher than those achieved in the oral group. The peak serum concentrations of INH, Z and RIF in the inhaled group were negligible and far lower than those for the oral group [Table 1].

As the first step, our study has demonstrated that inhaled ATDs attain appreciably higher levels in the ELF and AM as compared to orally administered drugs. Similarly, inhaled drug administration is associated with lower serum concentrations. Studies on multiple dose pharmacokinetics are required to further investigate our findings.


 :: Acknowledgment Top


  1. Lupin Pharmaceuticals, Inc., India for providing Pharmacopeial form of drugs
  2. Medispan pvt ltd., India for providing Drug manufacturing facility


 
 :: References Top

1.Pandey R, Khuller GK. Antitubercular inhaled therapy: Opportunities, progress and challenges. J Antimicrob Chemother 2005;55:430-5.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Lipworth BJ. New perspectives on inhaled drug delivery and systemic bioactivity. Thorax 1995;50:105-10.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]



 
 
    Tables

  [Table 1]

This article has been cited by
1 Nanopolymersomes as potential carriers for rifampicin pulmonary delivery
Marcela A. Moretton,Maximiliano Cagel,Ezequiel Bernabeu,Lorena Gonzalez,Diego A. Chiappetta
Colloids and Surfaces B: Biointerfaces. 2015; 136: 1017
[Pubmed] | [DOI]
2 Inhaled Solid Lipid Microparticles to target alveolar macrophages for tuberculosis
Eleonora Maretti,Tiziana Rossi,Moreno Bondi,Maria Antonietta Croce,Miriam Hanuskova,Eliana Leo,Francesca Sacchetti,Valentina Iannuccelli
International Journal of Pharmaceutics. 2014; 462(1-2): 74
[Pubmed] | [DOI]
3 The Influence of Feedstock and Process Variables on the Encapsulation of Drug Suspensions by Spray-Drying in Fast Drying Regime: The Case of Novel Antitubercular Drug-Palladium Complex Containing Polymeric Microparticles
Stefano Giovagnoli,Francesco Palazzo,Alessandro Di Michele,Aurelie Schoubben,Paolo Blasi,Maurizio Ricci
Journal of Pharmaceutical Sciences. 2014; 103(4): 1255
[Pubmed] | [DOI]
4 In Silico children and the glass mouse model: Clinical trial simulations to identify and individualize optimal isoniazid doses in children with tuberculosis
Jeena, P.M., Bishai, W.R., Pasipanodya, J.G., Gumbo, T.
Antimicrobial Agents and Chemotherapy. 2011; 55(2): 539-545
[Pubmed]
5 An oracle: Antituberculosis pharmacokinetics-pharmacodynamics, clinical correlation, and clinical trial simulations to predict the future
Pasipanodya, J., Gumbo, T.
Antimicrobial Agents and Chemotherapy. 2011; 55(1): 24-34
[Pubmed]
6 Penetration of Anti-Infective Agents into PulmonaryEpithelial Lining Fluid : Focus on Antifungal, Antitubercular and Miscellaneous Anti-Infective Agents
Keith A. Rodvold, Liz Yoo, Jomy M. George
Clinical Pharmacokinetics. 2011; 50(11): 689
[VIEW] | [DOI]
7 New susceptibility breakpoints for first-line antituberculosis drugs based on antimicrobial pharmacokinetic/pharmacodynamic science and population pharmacokinetic variability
Gumbo, T.
Antimicrobial Agents and Chemotherapy. 2010; 54(4): 1484-1491
[Pubmed]



 

Top
Print this article  Email this article
Previous article Next article
Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow