Document Detail


Absolute bioavailability and absorption characteristics of aerosolized tobramycin in adults with cystic fibrosis.
MedLine Citation:
PMID:  8021334     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Administration of antibiotics by the inhalational route has become part of standard protocols for treatment of and prophylaxis for Pseudomonal pneumonias in patients with cystic fibrosis. For tobramycin, however, limited data are available on the aerosol absorption patterns, and no absolute bioavailability data for tobramycin exist. The purpose of this study was to measure the absolute bioavailability and systemic absorption characteristics of tobramycin when administered in high doses by a nebulizer. Multiple serum concentrations of tobramycin were measured after administration of an intravenous dose (mean, 2.9 mg/kg every 6 hours) and after an inhalational dose (5.6 mg/kg over 1 hour). Inhalational doses were superimposed over the "tail" of a steady-state intravenous dose to improve the sensitivity of the assay procedure (Abbott-TDX). Absolute bioavailability (F) was determined from AUC ratios normalized for dose. Model-independent pharmacokinetic parameters (volume of distribution [Vss] and total clearance [CLt]) were determined for each subject. Absorption characteristics (absorption rate constant [Ka] and mean absorption time [MAT]) were assessed after calculation of the cumulative fraction of drug absorbed, amount of bioavailable drug, and percent remaining to be absorbed per unit time using the Loo-Riegelman method. Three men and three women completed the study, and all received concurrent doses of ceftazidime. Mean absolute bioavailability (+/- standard deviation) was 9.13% (+/- 3.82), and the rate of absorption into the systemic circulation was consistent with a zero-order model profile for all subjects. Mean absorption time values reflected a wide degree of subject variability and ranged from approximately 15 to 150 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
G F Cooney; B L Lum; M Tomaselli; S B Fiel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  34     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  1994 Mar 
Date Detail:
Created Date:  1994-08-04     Completed Date:  1994-08-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  255-9     Citation Subset:  IM    
Affiliation:
Temple University School of Pharmacy, Philadelphia, PA 19140.
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MeSH Terms
Descriptor/Qualifier:
Administration, Inhalation
Adult
Aerosols
Biological Availability
Ceftazidime / administration & dosage
Cystic Fibrosis / blood,  metabolism*
Female
Humans
Intestinal Absorption
Male
Metabolic Clearance Rate
Nebulizers and Vaporizers
Tobramycin / administration & dosage,  blood,  pharmacokinetics*
Grant Support
ID/Acronym/Agency:
RR 349/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Aerosols; 32986-56-4/Tobramycin; 78439-06-2/Ceftazidime

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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