Smoking and Theophylline Dose Schedules

Ri, Ogilvie

doi:10.7326/0003-4819-88-2-263_2

Cited by 10 publications

(4 citation statements)

References 7 publications

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“…This very small pro portion of patients with concentrations within the toxic range was virtually ident ical to the 2.8% found by Paterson et al [37]. The results clearly showed generally lower theophylline concentrations in smoking than in non-smoking patients, and this finding is in keeping with previ ous reports on the effect of smoking on theophylline metabolism [17][18][19][20], The rela tive efficacy of the three preparations is il lustrated in figures 1-4. Overall, the results between preparations, and at a normal dosage of 600-700 mg/day, show a statis tically significant difference in favour of Theolair Retard over Theolin Retard and Theograd.…”

Section: Comparison O F Sustained-release Theophylline Preparationssupporting

confidence: 80%

“…Patients are usually hospitalised in-patients [14][15][16], and both the patients or volunteers selected, as well as the conditions of the study, are careful ly controlled. For example, diet is often restricted to avoid xanthine-containing food and drinks on blood sampling days, patients are rested in hospital wards or in out-patient clinics rather than being ac tive, smoking is controlled or selected groups of smokers/non-smokers only are used [17][18][19][20]. The very presence of the pa tient in hospital is itself a 'special condi tion' and affects, for example, his compli ance with drug regimes.…”

Section: Introductionmentioning

confidence: 99%

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Sustained-Release Theophylline Preparations

Steenhoek¹,

Palmen

1984

Respiration

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The comparative efficacy and patient compliance with treatment using three sustained-release theophylline preparations currently available in The Netherlands were evaluated by measuring the plasma concentration achieved in a survey of 282 hospital and 185 out-patients. Compliance was dramatically better amongst in-patients than those attending out-patient clinics. Complete treatment avoidance was higher than expected. Compliance was better among non-smokers than among patients who were still smoking. Patients clearly preferred preparations which permitted a simple daily dosing schedule requiring the minimum number of tablets. On this basis and that of the parameters measured, Theolair Retard was the preparation of choice. Plasma concentration should be monitored during long-term theophylline treatment.

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Section: Comparison O F Sustained-release Theophylline Preparationssupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Sustained-Release Theophylline Preparations

Steenhoek¹,

Palmen

1984

Respiration

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“…This raises the possibility that increasing age may decrease the responsiveness of hepatic drug metabolising enzymes to stimulants such as cigarette smoke (Jusko, 1978). A major un-279 answered question is the time to recovery after induction of theophylline by smoking (Ogilvie, 1978). A kinetic study of the effect of smoking on theophylline disposition in the elderly should be carried out as well as a study of the rate of recovery from the stimulated state upon cessation from smoking in a large and varied study population.…”

Section: Smoking Habitsmentioning

confidence: 99%

Clinical Pharmacokinetics of Theophylline

Ogilvie

1978

Clinical Pharmacokinetics

435

142

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Knowledge acquired of the kinetic disposition and effects of theophylline over the past 8 years has increased the clinical utility of the drug in the treatment of cardiorespiratory disorders. Although the anhydrous theophylline content varies greatly between products, there is similar excellent oral bioavailability. An average 96 % (range 75 to 105 %) of an uncoated theophylline tablet is absorbed, with peak concentrations occurring from 0.5 to 2.0h. Enteric coated and many sustained release preparations have poor bioavailability. Intravenous preparations of aminophylline contain from 75 to 85 % theophylline by weight. Other routes of administration are not to be recommended . . In plasma, some 53 to 65 % of theophylline is reversibly bound to protein. Premature neonates and adults with hepatic cirrhosis have reduced binding. The apparent volume of distribution in the steady state averages 0.5L/ kg body weight regardless of sex, age (J to 87 years), history of cigarette smoking, asthma, or acute pulmonary oedema. Premature neonates and adults with acidaemia, hepatic cirrhosis or obesity tend to have larger volumes of distribution for theophylline.Theophylline is eliminated by biotransformation in the liver and urinary excretion of its metabolites. Approximately 7 to 13 % is excreted unchanged in the urine by a first order process. One of the metabolites, 3 -methylxanthine, which is pharmacologically active but less potent than theophylline, is eliminated by Michaelis-Menten kinetics. Removal of dietary methylxanthines can increase the rate of elimination of a single dose of theophylline. Dose dependent elimination kinetics has been suggested but not conclusively demonstrated.The plasma theophylline concentration time curve after intravenous administration fits a 2 compartment open kinetic model with a rapid a distribution phase completed within 30 to 45 minutes after an intravenous dose. The ~ elimination phase (t 1I2~ is quite variable and in healthy adults ranges from 3 to 13h. As the apparent volume of distribution is little altered under most conditions, variations in theophylline elimination half-life reflect alterations in plasma theophylline clearance. The predominant factors which alter theophylline clearance are age, body weight, diet, smoking habits, other drugs and cardiorespiratory or hepatic disease.The elimination of theophylline is markedly decreased in premature infants and increased in childhood. The rapid clearance in childhood decreases toward adult values in the late teens. Some authors believe old age per se decreases an individual's capacity to eliminate theophylline. However, this may be a reflection of the inability of hepatic enzymes in the elderly to respond to factors in the diet or environment which usually stimulate theophylline clearance.The elimination half-life of theophylline is prolonged in obese subjects and maintenance doses must be calculated from ideal body weight. Theophylline clearance can be decreased by a high carbohydrate-low protein diet, as well as the ingestion of oth...

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“…The enhanced theophylline clearance in smokers has been attributed to enzyme induction (Hunt et al, 1976), although the effect is more marked than that of smoking on the metabolism of other drugs (Miller, 1977). Heavy smokers who quit the habit may still have enhanced theophylline clearance as long as two years later (Ogilvie, 1978b), an observation suggesting that smoking might not be the proximate cause of the altered metabolism. We observed higher theophylline concentrations, and a trend to increased toxicity, in patients with low serum transaminases.…”

Section: Factors Related To Plasma Theophylline Concentrationmentioning

confidence: 99%

Oral sustained‐release aminophylline in medical inpatients: factors related to toxicity and plasma theophylline concentrations.

Ramsay¹,

Mackay²,

Eppel³

et al. 1980

Brit J Clinical Pharma

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1 Consecutive medical inpatients expected to benefit from a theophyllinate were treated with sustained-release aminophylline in a protocol conforming with ordinary practice. Of 16 patients, five had toxicity with aminophylline 450 mg daily, and a further three with 900 mg daily. Toxicity was serious in three patients. 2 Toxicity was significantly less common in cigarette smokers, and was related to higher plasma theophylline concentrations. However, there was a large overlap between concentrations associated with toxicity (as low as 9 pg/ml) and the accepted therapeutic range (5-20 pg/ml). Most patients with toxicity had theophylline levels within the therapeutic range. 3 For the same dose of aminophylline there was sevenfold variation between patients in plasma theophylline, with higher conentrations in non-smokers, infrequent alcohol users, older patients, those with left ventricular failure and those with lower serum transaminases. These variables could not be separated completely because of the small number of observations. 4 A nomogram for aminophylline dosage or monitoring of serum theophylline levels would have prevented little of the toxicity observed in these patients, although these measures would ensure that therapeutic concentrations were attained, and might prevent life-threatening toxicity.

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Smoking and Theophylline Dose Schedules

Cited by 10 publications

References 7 publications

Sustained-Release Theophylline Preparations

Sustained-Release Theophylline Preparations

Clinical Pharmacokinetics of Theophylline

Oral sustained‐release aminophylline in medical inpatients: factors related to toxicity and plasma theophylline concentrations.

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