Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Theophylline and its derivatives, such as aminophylline, have an established role as bronchodilators, although their mode of action in man is not clear. There is circumstantial evidence that therapeutic doses of theophylline may have a phosphodiesterase inhibiting effect, thus potentiating the effects of cyclic AMP. However, it remains to be established whether this is the primary mode of action of theophylline at the biochemical level. The pathways of theophylline metabolism have been clarified, although most of the enzymes involved have not been characterized. Hepatic microsomal enzyme induction by polycyclic hydrocarbons will increase the rate of theophylline elimination. There are a number of factors which influence theophylline clearance in adults, which is known to be highly variable. These factors include obesity, smoking habit, diet and the presence of such diseases as hepatic cirrhosis, acute pulmonary oedema, cor pulmonale and viral respiratory infection. There is a good correlation between plasma theophylline level and bronchodilator effect. This can be demonstrated at plasma levels as low as 5 microgram/ml, although optimal levels are usually greater than 10 microgram/ml. Unacceptable toxicity usually occurs in association with plasma levels greater than 20 microgram/ml. The maintenance of adequate plasma theophylline levels by the use of a sustained-release aminophylline tablet is discussed.
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PMID:Theophylline: biochemical pharmacology and pharmacokinetics. 22 Jan 19

The effect of obesity on the serum protein binding of theophylline was investigated in man and rat along with other ancillary variables such as dialysis time, theophylline concentration, albumin concentration, and fatty acid type and concentration. The percent binding of theophylline first increased with dialysis time, reached equilibrium over 2 to 6 h, then diminished. This decrease was not due to instability of theophylline. Theophylline binding was linear over a concentration range of 15 to 150 micrograms ml-1. A similar degree of binding was found in normal humans (44.4 +/- 1.0%) and rats (41.5 +/- 0.5%). The binding ratio (bound/free) of theophylline was proportional to the albumin concentration (1 to 5%) and yielded a binding parameter (NK) of 1.47 x 10(-3) M-1. Over a normal physiological range, individual and mixed fatty acids had minimal effects on theophylline binding to albumin. However, binding significantly decreased as fatty acid (FFA) concentrations increased. The magnitude of the effect appeared to parallel the carbon chain number of the fatty acid. Theophylline binding in obese subjects decreased to a mean (SD) of 35.8 +/- 8.0 per cent compared to 43.0 +/- 6.1 per cent in normal subjects (p less than 0.05). Similar decreases were found in normal versus obese rats and in the saliva: serum ratio following theophylline administration to normal and obese human subjects. Obesity causes a moderate decrease in serum binding of theophylline which may be attributed to increased FFA rather than in vitro artifacts.
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PMID:Effects of obesity and ancillary variables (dialysis time, drug, albumin, and fatty acid concentrations) on theophylline serum protein binding. 261 56

Theophylline plasma levels and FEV1 were measured in patients affected by chronic obstructive pulmonary disease and a concomitant disease state (congestive heart failure, chronic cor pulmonale, obesity, peptic disease, hepatic cirrhosis, chronic renal failure) and treated with a sustained release theophylline preparation. Our results indicate that, only in patients affected by congestive heart failure and chronic cor pulmonale, is there a decreased plasma clearance of the drug. Low levels of plasma theophylline were measured in obese patients probably because they received an inadequate posology.
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PMID:Effect of various disease states on theophylline plasma levels and on pulmonary function in patients with chronic airway obstruction treated with a sustained release theophylline preparation. 330 82

Theophylline tissue distribution was examined in normal and dietary-induced obese Sprague-Dawley rats following constant infusion to steady-state. Theophylline distribution was linear among all tissues and uniform throughout body water spaces. The apparent distribution coefficient, Kd,app (tissue: serum concentration) ranged from 0.55 to 0.69 for all lean tissues, but averaged 0.08 in fat. Obese rats had a consistently higher Kd,app in several tissues including muscle, heart, and liver caused by reduced (from 42 to 33 per cent) serum protein binding. Muscle slice uptake of theophylline from buffer was similar in normal and obese animals, confirming serum binding as the factor altering Kd,app. The conceptual and applied bases of calculating and measuring steady-state volume of distribution (VSS) by various methods were explored. The physiological perturbations of theophylline VSS by obesity can be accounted for by alterations in serum binding and expanded lean and fat tissue masses, rather than changes in tissue partitioning.
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PMID:Theophylline tissue partitioning and volume of distribution in normal and dietary-induced obese rats. 362 May 94

A dietary-induced animal model of obesity was examined to assess the mechanisms of obesity-altered changes in theophylline clearance and distribution. Obesity was induced over several months in Sprague-Dawley rats by feeding a palatable "cafeteria" diet containing approximately 60% fat in addition to normal chow (6% fat). Body composition (fat volume and fat-free mass) was measured by a standard tritium dilution method. Obese male rats achieved body weights up to 55% larger than normal controls. Theophylline disposition was not affected by the cafeteria diet or ages of the animals. Theophylline was measured in serum by high-performance liquid chromatography after a 20-mg/kg i.v. dose of drug, and total clearance and steady-state volume of distribution (Vss) were calculated. Absolute clearance (uncorrected for body size parameters) was similar in normal (26.8 +/- 5.4 ml/h) and obese (22.5 +/- 3.6 ml/h) male rats, indicating that total metabolic function remained constant in spite of increased body and liver weights. The Vss increased proportionally with total body weight (0.42-0.48 ml/g). Analysis of drug in fat (partition coefficient = 0.091) indicated limited fat uptake of theophylline. The increase of fat-free mass in obesity was found to account for similar Vss per gram values between normal and obese animals. The diet failed to induce obesity in female rats and the latter exhibited lower drug clearances, even upon adjustment for body weight. The dietary obese male rat resembles the human with respect to theophylline pharmacokinetics and allows demonstration of appropriate normalization of parameters for abnormal body weights under controlled experimental conditions.
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PMID:Theophylline disposition in obese rats. 669 16