Absolute bioavailability and absorption characteristics of aerosolized tobramycin in adults with cystic fibrosis

G. F. Cooney, B. L. Lum, M. Tomaselli, Stanley Fiel

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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 [V(ss)] 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. The authors conclude that there is limited uptake of tobramycin into the systemic circulation when administered by nebulizer aerosol into the lungs even in high doses. Absorption of tobramycin from the alveolar space into the pulmonary vasculature appears to be rate limited, but this may be characteristic for adults with cystic fibrosis. The authors also conclude that high doses of tobramycin administered by aerosolized nebulizer in these patients would contribute little to the risk of toxicity because of the poor systemic uptake of this drug.

Original languageEnglish (US)
Pages (from-to)255-259
Number of pages5
JournalJournal of Clinical Pharmacology
Volume34
Issue number3
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Tobramycin
Cystic Fibrosis
Biological Availability
Nebulizers and Vaporizers
Aerosols
Pharmaceutical Preparations
Lung
Ceftazidime
Clinical Protocols
Intravenous Administration
Area Under Curve
Pneumonia
Pharmacokinetics
Anti-Bacterial Agents
Serum

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

@article{105c97f47c054fd0af1777e7769cc396,
title = "Absolute bioavailability and absorption characteristics of aerosolized tobramycin in adults with cystic fibrosis",
abstract = "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 [V(ss)] 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. The authors conclude that there is limited uptake of tobramycin into the systemic circulation when administered by nebulizer aerosol into the lungs even in high doses. Absorption of tobramycin from the alveolar space into the pulmonary vasculature appears to be rate limited, but this may be characteristic for adults with cystic fibrosis. The authors also conclude that high doses of tobramycin administered by aerosolized nebulizer in these patients would contribute little to the risk of toxicity because of the poor systemic uptake of this drug.",
author = "Cooney, {G. F.} and Lum, {B. L.} and M. Tomaselli and Stanley Fiel",
year = "1994",
month = "1",
day = "1",
doi = "10.1002/j.1552-4604.1994.tb03995.x",
language = "English (US)",
volume = "34",
pages = "255--259",
journal = "Journal of Clinical Pharmacology",
issn = "0091-2700",
publisher = "SAGE Publications Inc.",
number = "3",

}

Absolute bioavailability and absorption characteristics of aerosolized tobramycin in adults with cystic fibrosis. / Cooney, G. F.; Lum, B. L.; Tomaselli, M.; Fiel, Stanley.

In: Journal of Clinical Pharmacology, Vol. 34, No. 3, 01.01.1994, p. 255-259.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Absolute bioavailability and absorption characteristics of aerosolized tobramycin in adults with cystic fibrosis

AU - Cooney, G. F.

AU - Lum, B. L.

AU - Tomaselli, M.

AU - Fiel, Stanley

PY - 1994/1/1

Y1 - 1994/1/1

N2 - 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 [V(ss)] 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. The authors conclude that there is limited uptake of tobramycin into the systemic circulation when administered by nebulizer aerosol into the lungs even in high doses. Absorption of tobramycin from the alveolar space into the pulmonary vasculature appears to be rate limited, but this may be characteristic for adults with cystic fibrosis. The authors also conclude that high doses of tobramycin administered by aerosolized nebulizer in these patients would contribute little to the risk of toxicity because of the poor systemic uptake of this drug.

AB - 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 [V(ss)] 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. The authors conclude that there is limited uptake of tobramycin into the systemic circulation when administered by nebulizer aerosol into the lungs even in high doses. Absorption of tobramycin from the alveolar space into the pulmonary vasculature appears to be rate limited, but this may be characteristic for adults with cystic fibrosis. The authors also conclude that high doses of tobramycin administered by aerosolized nebulizer in these patients would contribute little to the risk of toxicity because of the poor systemic uptake of this drug.

UR - http://www.scopus.com/inward/record.url?scp=0028343935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028343935&partnerID=8YFLogxK

U2 - 10.1002/j.1552-4604.1994.tb03995.x

DO - 10.1002/j.1552-4604.1994.tb03995.x

M3 - Article

C2 - 8021334

AN - SCOPUS:0028343935

VL - 34

SP - 255

EP - 259

JO - Journal of Clinical Pharmacology

JF - Journal of Clinical Pharmacology

SN - 0091-2700

IS - 3

ER -