1990
DOI: 10.2165/00003088-199019060-00004
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The Effect of Respiratory Disorders on Clinical Pharmacokinetic Variables

Abstract: Respiratory disorders induce several pathophysiological changes involving gas exchange and acid-base balance, regional haemodynamics, and alterations of the alveolocapillary membrane. The consequences for the absorption, distribution and elimination of drugs are evaluated. Drug absorption after inhalation is not significantly impaired in patients. With drugs administered by this route, an average of 10% of the dose reaches the lungs. It is not completely clear whether changes in pulmonary endothelium in respir… Show more

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Cited by 22 publications
(9 citation statements)
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(18 reference statements)
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“…It is worth noting, however, that the PK of pulmonary administered proteins may be altered in the disease state. Factors such as altered alveolar permeability and vasculature remodeling, infiltration of immune cells, and changes to respiratory mucus lining may influence the absorption and clearance of proteins from the lungs . This will need to be investigated prior to translation into humans.…”
Section: Discussionmentioning
confidence: 99%
“…It is worth noting, however, that the PK of pulmonary administered proteins may be altered in the disease state. Factors such as altered alveolar permeability and vasculature remodeling, infiltration of immune cells, and changes to respiratory mucus lining may influence the absorption and clearance of proteins from the lungs . This will need to be investigated prior to translation into humans.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, with a shift from aerobic to anaerobic metabolism, there may occur a fall in pH [7]. Local pH conditions in the cell can also contribute to an alteration in clinical effect or metabolism [24, 25]. …”
Section: Acute Effects Of Hypoxiamentioning
confidence: 99%
“…However, once the hypoxia progresses to the point in which oxygen delivery to the myocardium cannot be maintained, there may be a precipitous and critical decrease in cardiac output and myocardial blood flow with attendant bradycardia and hypotension 6. The mechanisms by which these processes could influence the disposition of drugs therefore include: (1) circulatory changes altering blood flow to organs of distribution or metabolism, (2) changes in pH influencing protein binding and distribution volumes, and (3) reduced rates of drug metabolism by cytochrome P450 enzymes, for which oxygen is a substrate 4…”
Section: Introductionmentioning
confidence: 99%
“…A systematic analysis requires a knowledge of the physiological factors influencing the disposition of drugs, and how these are affected by the individual disease processes that may comprise critical illness in an individual patient. Hypoxia is one of these processes, and previous workers have studied its effects on drug disposition 4. However, it is difficult to make general conclusions because of the variety of physiological states produced by hypoxia.…”
Section: Introductionmentioning
confidence: 99%