Relationship Between Serum and Saliva Theophylline Levels in Patients with Cystic Fibrosis

Blanchard, James; Harvey, Suzanne; Morgan, Wayne J.

doi:10.1097/00007691-199202000-00008

Cited by 9 publications

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“…In previous studies, we have analysed specific pro-inflammatory markers in chronic and severe inflammatory lung diseases in order to detect pathognomonic patterns for the underlying disease [ 18 , 38 – 45 ]. The knowledge that chronic inflammation is harmful to the CF lung has resulted in strategies to reduce lung infection [ 46 ] and the damage associated with chronic inflammation [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis

et al. 2017

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BackgroundCystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF.MethodsIn this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach.ResultsDHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05).ConclusionsSPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was present in sputum and plasma of CF patients and may serve as a representative peripheral biomarker of the lung resolution program for CF patients.

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Section: Discussionmentioning

confidence: 99%

Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis

et al. 2017

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“…Taking theophylline as an example, it has been postulated that saliva levels representing a "natural ultrafiltrate" allow prediction of the unbound serum theophylline concentration with greater accuracy and precision than they predict total serum concentration, especially in disease states such as cystic fibrosis or asthma bronchiale (36). These are summarized Brought to you by | University of Queensland -UQ Library Authenticated Download Date | 6/22/15 7:01 PM in table 4.…”

Section: Protein Bindingmentioning

confidence: 99%

“…Both drugs have relatively low lipid solubility. Other examples are lidocaine, procainamide (40), theophylline (36,51) and cocaine (52). These compounds have also been called "low clearance drugs" or drugs with a low extraction ratio (26).…”

Section: Flow Ratementioning

confidence: 99%

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1996

CCLM

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The determination of salivary drug concentrations is one of the major domains for the application of saliva in laboratory medicine. Its usefulness, however, has been criticized for many drugs because of the variability of the saliva/plasma concentration ratio (saliva/plasma ratio).Considering saliva as a model for transmembrane transport, drugs can be divided into 4 groups. The first group is characterized by a saliva/plasma ratio less than 1.0. In extreme cases a drug with negligible transport is either not detectable in saliva or is found in very low concentrations which are hard to measure or difficult to interpret.A second group leads to saliva/plasma ratios which are approximately constant and about 1.0 under most of the conditions studied. This group is ideal for monitoring salivary drug concentrations.A third group is sufficiently transferred into saliva, but the saliva/plasma ratio varies under different conditions. The reason for this variation is that the transport is influenced by several factors including an active transport mechanism. The varying influence of these factors on the saliva/plasma ratio largely depends on the physicochemical characteristics of the particular substance.In a fourth group very high saliva/plasma ratios are observed primarily due to the degree of ionization of weak bases.A representative of each group is presented with its saliva/plasma ratio and its physico-chemical properties: ceftazidim, ethanol, digoxin and prilocain. In all cases the salivary concentration probably reflects the intracellular concentration in target tissues. All examples confirm saliva as an ideal in vivo model for the study of transmembrane transport in the human organism.

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Pharmacokinetics and Metabolism of Natural Methylxanthines in Animal and Man

Arnaud

2010

Handbook of Experimental Pharmacology

209

228

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Caffeine, theophylline, theobromine, and paraxanthine administered to animals and humans distribute in all body fluids and cross all biological membranes. They do not accumulate in organs or tissues and are extensively metabolized by the liver, with less than 2% of caffeine administered excreted unchanged in human urine. Dose-independent and dose-dependent pharmacokinetics of caffeine and other dimethylxanthines may be observed and explained by saturation of metabolic pathways and impaired elimination due to the immaturity of hepatic enzyme and liver diseases. While gender and menstrual cycle have little effect on their elimination, decreased clearance is seen in women using oral contraceptives and during pregnancy. Obesity, physical exercise, diseases, and particularly smoking and the interactions of drugs affect their elimination owing to either stimulation or inhibition of CYP1A2. Their metabolic pathways exhibit important quantitative and qualitative differences in animal species and man. Chronic ingestion or restriction of caffeine intake in man has a small effect on their disposition, but dietary constituents, including broccoli and herbal tea, as well as alcohol were shown to modify their plasma pharmacokinetics. Using molar ratios of metabolites in plasma and/or urine, phenotyping of various enzyme activities, such as cytochrome monooxygenases, N-acetylation, 8-hydroxylation, and xanthine oxidase, has become a valuable tool to identify polymorphisms and to understand individual variations and potential associations with health risks in epidemiological surveys.

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Relationship Between Serum and Saliva Theophylline Levels in Patients with Cystic Fibrosis

Cited by 9 publications

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Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis

Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis

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Pharmacokinetics and Metabolism of Natural Methylxanthines in Animal and Man

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