Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/8804
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Type: Journal article
Title: The effect of hypoxaemia on drug disposition in chronic respiratory failure
Author: Rowett, D.
Latimer, K.
Sansom, L.
Ruffin, R.
May, F.
Henderson, G.
Hayball, P.
Citation: European Journal of Clinical Pharmacology, 1996; 50(1):77-82
Publisher: Springer-Verlag
Issue Date: 1996
ISSN: 0031-6970
1432-1041
Statement of
Responsibility: 
D. Rowett, K. Latimer, L. N. Sansom, R. E. Ruffin, F. May, G. Henderson, P. J. Hayball
Abstract: Objective: The influence of hypoxaemia on the disposition of two common drugs has been examined in ten adults with stable chronic respiratory failure. Methods: There were two experimental periods in this cross-over study: during these periods supplemental oxygen was either withheld or administered to impose clinical hypoxaemia or maintain normoxaemia, respectively. Each participant received either oral (40 mg) or intravenous (20 mg) frusemide combined with oral paracetamol (500 mg) on consecutive days of the two experimental periods. Results: The total (bound plus unbound) plasma clearance of frusemide during hypoxaemia (arterial oxygen tension, PaO2 ≤ 50 Torr) was not significantly different from the value during normoxaemia (PaO2 ≥ 60 Torr) [76.9 and 62.4 ml ⋅ min−1]. The volume of distribution was not affected by acute hypoxaemia (121 ml ⋅ kg−1 without and 109 ml ⋅ kg−1 with oxygen; P > 0.05). Renal and non-renal clearances of frusemide were similar during the period of hypoxaemia (31 and 38 ml ⋅ min−1, respectively) compared to respective values during supplemental oxygen delivery (29 and 32 ml ⋅ min−1). The absolute bioavailability of frusemide during hypoxaemia (0.62) was not different to that obtained during normoxaemia (0.56). The combined sodium and potassium excretion rate (expressed as a function of the frusemide excretion rate) was not altered by changing the oxygen tension. The pharmacokinetics of paracetamol were unaffected by hypoxaemia.
Keywords: Humans
Respiratory Insufficiency
Chronic Disease
Acetaminophen
Furosemide
Analgesics, Non-Narcotic
Hypoglycemic Agents
Cross-Over Studies
Protein Binding
Oxygen Consumption
Biological Availability
Adult
Aged
Middle Aged
Female
Male
Hypoxia
Rights: © Springer-Verlag 1996
DOI: 10.1007/s002280050072
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