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  • 1
    Electronic Resource
    Electronic Resource
    Greatly enhanced bioavailability of theophylline on postprandial administration of a sustained release tablet (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 761-767 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; bioavailability ; sustained release tablet ; pharmacokinetics ; Theograd-250
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of theophylline after oral administration of a new sustained release tablet Theograd®-250 mg was studied in 7 healthy volunteers, under fasting and non-fasting conditions. Whilst fasting the bioavailability was moderate at 64±22% (mean±SD), whereas in the non-fasting state the relatively high bioavailability of 90±13% was found. The drug appeared to be significantly more slowly absorbed when a tablet was taken after a meal, than when it was ingested on an empty stomach. In the former case, the peak level was reached after 6.9±1.0 h, whereas in the fasting state the maximum serum concentration occurred 4.0±1.7 h after administration of the drug. Despite the slow absorption, the peak non-fasting level of 4.4±1.4 mg·l−1 was significantly higher than the 3.1±1.0 mg·l−1 observed in the fasting state. The profiles of the serum concentration-time curves showed that the concentration remained above 75% of Cmax for 8.7±1.3 h in the fasting and 9.0±1.1 h in the non-fasting state. It was concluded that to define the optimal dosage regime for sustained release oral dosage forms of theophylline, the influence of food on absorption from these preparations should be taken into account. Based on the present results, Theograd®-250 mg tablets have predictable absorption and a high (90%) bioavailability if taken after a meal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607084
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  • 2
    Electronic Resource
    Electronic Resource
    Disposition and clinical pharmacokinetics of microcrystalline theophylline (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558452
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  • 3
    Electronic Resource
    Electronic Resource
    Correlation of serum and saliva theophylline concentrations after administration of a sustained release preparation (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 73-78 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; sustained release preparation ; serum level ; saliva level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The correlation between serum and saliva levels of theophylline was investigated in seven healthy volunteers after multiple dose administration of a low dose (300 mg/day) and a high dose (900 mg/day) of a sustained release theophylline preparation (Theo-Dur®). Tablets were taken for five days, at 8 a.m. and 8 p.m. and a last dose was taken on Day 6 at 8 a. m. Fourteen serum and saliva samples were collected simultaneously during the dosing period and for up to 32 h after the last dose. On the 300 mg/day regimen the level in saliva was 55.3% of the serum level, with an overall variability of 6.7% and an intrasubject variability of 10.5%. After 900 mg/day, the saliva concentration was 55.5% of the serum concentration, with an overall variability of 7.6% and an intrasubject variability of 12.7%. A good correlation was found between both determinations (r=0.99), which suggests that saliva levels could be used to monitor theophylline after administration of a sustained release tablet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00554670
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  • 4
    Electronic Resource
    Electronic Resource
    Disposition and clinical pharmacokinetics of theophylline after administration of a new sustained release tablet (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 39-44 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; sustained release tablet ; absolute bioavailability ; pharmacokinetics ; individual dosage regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic disposition of theophylline after taking a new, sustained release tablet (Theolair Retard® 250 mg, Theolair S. R.®, Riker Laboratories) has been studied in 8 hospitalized patients. Absolute bioavailability was determined from the ratios of the areas under the serum concentration-time curves after intake of the tablet and after intravenous infusion of aminophylline in the same patient. The absolute bioavailability of Theolair Retard® 250 mg was 110.9±20.8% (mean ± SD). Maximal serum concentrations were reached after 7.3±3.5 h, the large intersubject variation being due to differences in gastric emptying time. The tablets appear to release theophylline slowly in acid conditions, but more rapidly in an alkaline medium. Invasion was found to be either monophasic with a rate constant of about 0.8 h−1 (intestine), or biphasic with rate constants of 0.2 h−1 (stomach) and 0.8 h−1 (intestine). The peak levels accounted for 7.9±2.2 mg · 1−1. The profiles of the serum concentration-time curves were such that the concentrations remained above 80% of cmax for 6.5±3.3 h. The relevant pharmacokinetic parameters (half-life of elimination, total body clearance and volume of distribution) were determined and were used to calculate the individual dosage regimens required to obtain therapeutic serum concentrations. The optimal dosing interval to obtain an average steady state serum concentration of 12.5 mg · l−1 was 9.8±3.1 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609586
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  • 5
    Electronic Resource
    Electronic Resource
    Protective effect of oral oxyphenonium bromide, terbutaline and theophylline against the bronchial obstructive effects of inhaled histamine, acetylcholine and propranolol (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 435-441 
    Details
    ISSN: 1432-1041
    Keywords: airway reactivity ; oxyphenonium bromide ; terbutaline ; theophylline ; asthmatic patients ; inhalation ; provocation test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protective effects of oxyphenonium bromide, terbutaline and theophylline were compared in 8 asthmatic patients by determination of the degree of non-specific airway reactivity after 1 week of oral treatment according to a fixed dose scheme in a double-blind random order: oxyphenonium bromide 3×10 mg; terbutaline 3×5 mg; theophylline 2×300 mg and placebo. Controlled, standardized inhalation provocation tests were carried out with histamine, acetylcholine and propranolol. The study was monitored by measuring blood concentrations of the 3 drugs, and their effect on the plasma cAMP concentration was also determined. Significant protection by oxyphenonium bromide against the bronchial obstructive effects of acetylcholine and propranolol was observed, but not against the effect of inhaled histamine. The other two drugs provided no significant protection against the inhaled agents. The absence of any protective effect of terbutaline and theophylline might have resulted from too low a blood concentration. The observed differences in protection could not be explained by changes in pulmonary function. The study suggests dissociation between the bronchodilating effect of a drug and its protective effect against inhaled substances.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542137
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  • 6
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis and in patients with chronic renal disease (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 357-362 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; enprofylline ; liver cirrhosis ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis, patients with chronic renal failure, and healthy subjects, and have assessed the predictive value of routine tests of liver function and renal function (creatinine clearance) for theophylline and enprofylline total body clearances. Theophylline clearance was significantly decreased in the patients with liver cirrhosis compared with both the patients with renal failure and the healthy subjects (the mean values in the three groups were 24, 47, and 46 ml·h−1·kg−1 respectively. Enprofylline clearance was significantly decreased in the patients with chronic renal failure, compared with both the patients with liver cirrhosis and the healthy subjects (the values in the three groups were 64, 250, and 289 ml·h−1·kg−1 respectively. There was a strong correlation between creatinine clearance and enprofylline clearance, while there was only a poor correlation between the liver function tests and theophylline clearance. It appears that in various clinical situations enprofylline elimination can be predicted more precisely than theophylline elimination, which may make the drug safer in clinical practice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561364
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  • 7
    Electronic Resource
    Electronic Resource
    Creation of four consecutive instantaneous steady-state plasma concentration plateaus of theophylline and enprofylline by repeated infusions with exponentially decreasing delivery rates (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 657-661 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; enprofylline ; asthma ; pharmacokinetics ; intravenous infusion ; plateau levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Repeated exponentially decreasing influsions have been used to administer theophylline and enprofylline to show whether it would be feasible to create consecutive plasma concentration plateaus within a few hours. The infusions were carried out on two separate days in 8 stable asthmatics. Before the infusion experiments, the pharmacokinetics of the substances in the individual subjects were determined on a separate day. Plasma concentration rose to the desired level within 5 min after the start of the infusion at each dose level and a stable plasma concentration plateau was maintained during the following 90 min of the infusion. It was possible to achieve 4 subsequent concentration plateaus within a 6 h period. Use of this infusion method resulted in predictable plasma concentrations at all levels and so the method appears safe when the required plasma concentrations are below the toxic level. Apart from clinical situations where effective dosages of drugs must be administered rapidly, the method showed be useful in pharmacological dose-response studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637603
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  • 8
    Electronic Resource
    Electronic Resource
    Food reduces the rate but not the extent of the absorption of theophylline from an aqueous solution (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 225-227 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; absorption ; food intake ; aqueous solution ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of food on the rate and extent of absorption of theophylline was studied in healthy adults given a single dose of theophylline (aqueous solution of choline theophyllinate containing 270 mg of theophylline) in the evening either on an empty stomach or together with supper. Food appeared to decrease the absorption rate of theophylline significantly, tmax being prolonged from 1.34 h (mean) to 4.40 h and cmax decreased from 7.82 mg·l−1 to 5.47 mg·l−1. The area under the plasma concentration-time curve (AUC) after drug intake with supper was slightly but not significantly smaller, indicating that theophylline (as a solution of choline theophyllinate) can be taken together with food without substantial loss of the quantity of drug absorbed. The elimination rate was not influenced by concomitant intake of supper.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609697
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  • 9
    Electronic Resource
    Electronic Resource
    Measurement of excretion characteristics of theophylline and its major metabolites (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 435-441 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; renal excretion ; metabolite formation ; capacity-limited kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Analysis of urinary excretion after administration of 320 mg of theophylline to six normal volunteers appears to indicate the occurrence of capacity limited formation of most of the theophylline metabolites and non-linear renal excretion of theophylline. The renal clearance is elevated at high concentrations where the metabolic clearance is reduced. Even though the individual process of elimination is non-linear, the compensating relationship appears to yield a constant total elimination clearance. The implication of these results in chronic therapy and dose adjustment is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542096
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