Pulmonary Disease and Drug Kinetics

Souich, Patrick du; McLean, Allan J.; Lalka, David; Erill, S.; Gibaldi, Milo

doi:10.2165/00003088-197803040-00001

Cited by 44 publications

(6 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results show that young children with minimal pathophysiological changes in liver and lung function have enhanced metabolism of the pathway involving CYP1A2 enzyme. Changes in liver function or pulmonary disease can affect drug metabolism,13 14 but these are more likely to result in impaired clearance, whereas patients with cystic fibrosis often have enhanced clearance of drugs. We have previously studied children with cystic fibrosis using the caffeine breath test7 and found it to be acceptable to both children and parents.…”

Section: Discussionmentioning

confidence: 99%

Enhanced drug metabolism in young children with cystic fibrosis

Parker

Pritchard²,

Preston³

et al. 1997

Archives of Disease in Childhood

View full text Add to dashboard Cite

The eVect of cystic fibrosis on caVeine metabolism was studied in young children using the caVeine breath test. Eight children with cystic fibrosis aged 2-6 years and nine age matched controls were studied on a single occasion, and the cumulative percentage of labelled caVeine exhaled as carbon dioxide measured over two hours. This was significantly higher in the patients with cystic fibrosis than in controls, suggesting an increase in the CYP1A2 metabolic pathway in the former. The fact that these were young children with minimal lung and liver disease suggests that enhanced drug metabolism in children with cystic fibrosis is hereditary rather than secondary to lung and liver damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhanced drug metabolism in young children with cystic fibrosis

Parker

Pritchard²,

Preston³

et al. 1997

Archives of Disease in Childhood

View full text Add to dashboard Cite

show abstract

“…Most pulmonary disease will result in altered arterial blood gas tension, hypoxia, acid-base imbalance or increased pulmonary vascular resistance (du Souich et al 1978). Most pulmonary disease will result in altered arterial blood gas tension, hypoxia, acid-base imbalance or increased pulmonary vascular resistance (du Souich et al 1978).…”

Section: Pulmonary Disease and Pharmacokineticsmentioning

confidence: 99%

“…Renal excretion of drugs may also be altered in pulmonary disease as a consequence of changes in plasma protein binding as well as a decrease in renal blood flow and glomerular filtration rate (du Souich et al 1978). Depending on their hepatic extraction characteristics, drugs that are primarily metabolised by the liver may also be expected to exhibit altered elimination in patients with pulmonary diseases.…”

Section: Pulmonary Disease and Pharmacokineticsmentioning

confidence: 99%

“…In humans, changes caused by respiratory disease on drug absorption, distribution, metabolism and elimination have been studied and reviewed for procainamide, corticosteroids, phenazone, tolbutamide, amikacin, amoxicillin, digoxin and ephedrine (du Souich et al 1978). In humans, changes caused by respiratory disease on drug absorption, distribution, metabolism and elimination have been studied and reviewed for procainamide, corticosteroids, phenazone, tolbutamide, amikacin, amoxicillin, digoxin and ephedrine (du Souich et al 1978).…”

Section: Pulmonary Disease and Pharmacokineticsmentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia, Arterial pH and Theophylline Disposition

Richer

Lam

1993

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Theophylline is a bronchodilator used extensively in the management of obstructive pulmonary disease. Factors implicated in altered theophylline clearance include smoking, age, concomitant drug intake, liver disease and left ventricular heart failure. However, evidence now suggests that theophylline clearance may be altered by changes in severity of the pulmonary obstruction, hypoxia and variation in arterial pH. The in vitro disposition of theophylline has been evaluated in isolated rat livers and mouse hepatocytes. In vivo studies have assessed the metabolism of theophylline under hypoxia in rats, rabbits and dogs. In isolated mouse hepatocytes and rat livers, low oxygen concentrations resulted in higher theophylline concentrations, a longer elimination half-life and a decrease in the production of the metabolite 1,3-dimethyl uric acid, suggesting impaired metabolism of theophylline. In rabbits, hypoxia, hypercapnia and respiratory acidosis decreased total body clearance and increased plasma theophylline concentrations. On the other hand, experiments involving dogs showed no significant changes in theophylline concentrations or pharmacokinetic parameters with hypoxia. At present, animal studies remain inconclusive. This can be attributed to the use of different animal models and variations in study methodology, including the extent and duration of hypoxia and acidaemia, concurrent acid-base disorders such as hypercapnia, as well as the severity of pulmonary obstruction. Human studies assessing alterations in theophylline disposition secondary to the hypoxia present in pulmonary disease are few and include mostly case reports and observational studies. There is evidence suggesting decreased theophylline clearance and protein binding during acute illness and some consensus can be achieved using case reports and controlled studies. There is additional evidence that drug clearance decreases with age and that elderly patients may have a decreased theophylline clearance at baseline. However, the most obvious markers appear to be the severity of pulmonary disease and the rate of change in the patient's condition. Caution should be exercised when administering theophylline to elderly patients with chronic obstructive pulmonary disease presenting with acute exacerbations of a concomitant respiratory illness, as these patients appear to be most likely to exhibit altered theophylline metabolism. Therefore, they would be at increased risk for toxicity should conventional dosages be used during an acute respiratory event.

show abstract

“…Not proven clinical importance: a longer half-life of amikacin is described in neonates with respiratory acidosis (du Souich et al, 1978). as it is for carbenicillin and clindamycin in serious liver disease (Bond, 1978;Blaschka, 1977); obesity or fasting can modify disposition of sulphonamides (Reidenberg, 1977).…”

Section: Tissue Penetration and Distributionmentioning

confidence: 99%

Clinical Relevance of Pharmacokinetics

Tognoni

Bellantuono

Bonati

et al. 1980

Clinical Pharmacokinetics

View full text Add to dashboard Cite

The importance of a more therapeutically oriented perspective for pharmacokinetics has been repeatedly advocated and stressed during the past few years. ReView of recent publications in this field reveals that the search for solutions to clinically relevant problems is merely a secondary goal in many studies. Hence, to obtain reliable information which can be applied safely in therapeutic practice. studies need to be interpreted critically. After careful analysis of publications on some of the most representative drugs and drug groups (anti-infective agents, antiepileptic drugs, psychotherapeutic drugs, antiarrhythmic agents, digoxin, propranolol, theophylline, warfarin, anticancer agents), tentative guidelines are given for datafor which the clinical relevance is well established, for findings for which the relevance should be checked in routine practice, for areas where much research is still needed before kinetic knowledge can result in improved therapeutic outcome, and for fields where only minor therapeutic advances can be expected fro,!, extended kinetic investigations. Within the general framework of clinical pharmacology, it appears that the use of pharmacokinetics is a fundamental research tool and a useful aid to therapeutic practice only if its limitations are clearly recognised, and if priority is given to creating favourable, controlled conditions for good diagnostic practice, general patient care and compliance of the patient with treatment. A restricted attitude is suggested toward the natural expansion of blood level monitoring, because of the risk that doctors and institutions become 'dependent' on this technique and 10lie their critical capacity in the use of both clinical and kinetic data.

show abstract

Pulmonary Disease and Drug Kinetics

Cited by 44 publications

References 57 publications

Enhanced drug metabolism in young children with cystic fibrosis

Enhanced drug metabolism in young children with cystic fibrosis

Hypoxia, Arterial pH and Theophylline Disposition

Clinical Relevance of Pharmacokinetics

Contact Info

Product

Resources

About