Dose Of Aminophylline Research Articles

Effect of passive smoking on theophylline clearance in children.

The author investigated the effects of passive tobacco smoking on the metabolism of theophylline in a pediatric population. In a retrospective analysis of 201 children admitted to a pediatric unit for asthma, 31 were identified with an acute exacerbation of asthma of noninfectious origin in which environmental exposure to tobacco smoke could be established. The parents were known smokers with a minimum 1-pack-per-day habit. An age-and gender-matched control population of children was then identified who had an acute exacerbation of asthma without any environmental exposure to tobacco smoke. In addition, the patients in both groups received the same dose of intravenous aminophylline for a minimum of 48 hours to ensure steady-state conditions. Total body clearance of theophylline was significantly elevated in the children exposed to environmental tobacco smoke (1.36 +/- 0.09 vs. 0.90 +/- 0.04 mL/min per kg, p < 0.0001). Steady-state serum levels were significantly lower in the passive smoking group (55.3 +/- 2.8 vs. 73.2 +/- 3.3 p < 0.00001) for those receiving nearly identical intravenous doses. The length of hospital stay was longer in the group exposed to passive smoke (4.4 +/- 2.6 vs. 2.9 +/- 1.3 days, p < 0.05). The clearance of theophylline is greater in asthmatic children exposed to passive tobacco smoke than in asthmatic children not exposed to passive tobacco smoke. These findings suggest that passive smoking may increase the clearance of other drugs metabolized in a manner similar to theophylline.

Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma.

Aminophylline has been used extensively in acute asthma, but its role is unclear especially with respect to any additional benefit when added to beta2-agonists. To determine the magnitude of effect of the addition of intravenous aminophylline to beta2-agonists in adult patients with acute asthma treated in the emergency setting. Studies were identified from the following sources: The Cochrane Airways Group register (derived from MEDLINE, EMBASE, CINAHL standardised searches), hand searched respiratory journals and meeting abstracts. Potentially relevant articles were obtained, and their bibliographic lists were hand searched for additional articles. The search included searches of the database up to 1999. Randomised controlled trials comparing intravenous aminophylline versus placebo in adults with acute asthma and treated with beta-adrenergic agonists. Patients could be treated with or without corticosteroids or other bronchodilators. A total of 210 abstracts were identified. Two independent reviewers selected a total of 27 eligible studies for possible inclusion, in which quality assessment was performed and a third reviewer was used to adjudicate disagreements. Peak expiratory flow (PEFR) and forced expiratory volume in the first second (FEV1) data were extracted and entered in Review Manager from these studies. Information not obtained from the authors was estimated from graphs. All data were entered and double checked by two reviewers. Results are reported as weighted mean differences (WMD) or odds ratio (OR), both with 95% confidential intervals (CI). Fifteen trials were included. Overall, the quality of the studies was only moderate; concealment of allocation was assessed as clearly adequate in only seven (45%) of the trials. The doses of aminophylline and other medications and the severity of asthma varied between studies. There was no statistically significant effect of aminophylline on airflow outcomes at any time period. The aminophylline treated group had higher values of PEFR at 12 (PEFR 8 L/min or 2.3%) and 24 hours (PEFR 22 L/min or 6.4%), but these were not significant (p>0.05). Two subgroup analyses were performed by grouping studies according to mean baseline airflow limitation (n = 11 studies) and the use of any steroids (n = 9 studies). There was no relationship between baseline airflow limitation nor the use of steroids on the effect of aminophylline. Aminophylline treated patients reported more palpitations/arrhythmias (OR: 2.9; 95% CI: 1.5 to 5.7) and vomiting (OR: 4.2; 95% CI 2.4 to 7.4), but no difference was found in tremor or hospital admissions. In acute asthma, the use of intravenous aminophylline did not result in any additional bronchodilation compared to standard care with beta-agonists. The frequency of adverse effects was higher with aminophylline. No subgroups in which aminophylline might be more effective could be identified. These results should be added to consensus statements and guidelines.

Role of adenosine in the hypoxia-induced hypothermia of toads.

The concept that hypoxia elicits a drop in body temperature (T(b)) in a wide variety of animals is not new, but the mechanisms remain unclear. We tested the hypothesis that adenosine mediates hypoxia-induced hypothermia in toads. Measurements of selected T(b) were performed using a thermal gradient. Animals were injected (into the lymph sac or intracerebroventricularly) with aminophylline (an adenosine receptor antagonist) followed by an 11-h period of hypoxia (7% O(2)) or normoxia exposure. Control animals received saline injections. Hypoxia elicited a drop in T(b) from 24.8 +/- 0.3 to 19. 5 +/- 1.1 degrees C (P < 0.05). Systemically applied aminophylline (25 mg/kg) did not change T(b) during normoxia, indicating that adenosine does not alter normal thermoregulatory function. However, aminophylline (25 mg/kg) significantly blunted hypoxia-induced hypothermia (P < 0.05). To assess the role of central thermoregulatory mechanisms, a smaller dose of aminophylline (0.25 mg/kg), which did not alter hypoxia-induced hypothermia systemically, was injected into the fourth cerebral ventricle. Intracerebroventricular injection of aminophylline (0.25 mg/kg) caused no significant change in T(b) under normoxia, but it abolished hypoxia-induced hypothermia. The present data indicate that adenosine is a central and possibly peripheral mediator of hypoxia-induced hypothermia.

Brain Hemodynamic Changes in Preterm Infants after Maintenance Dose Caffeine and Aminophylline Treatment

Objective: To investigate the acute effects of low-dose caffeine and aminophylline on cerebral blood flow in preterm infants, using both near-infrared spectroscopy (NIRS) and cerebral Doppler ultrasonography. Methods: Preterm infants with a gestational age of <32 weeks and birth weight of <1,500 g were randomized to receive either caffeine or aminophylline treatment for apnea of prematurity. The study period went from 30 min before to 60 min after the administration of the maintenance dose of pure caffeine (2.5 mg/kg once a day) or aminophylline (1.25 mg/kg twice a day). NIRS was used to measure changes in oxygenated hemoglobin (O₂Hb), deoxygenated hemoglobin (HHb), oxidized-reduced cytochrome aa3 (CtOx), and mean cerebral oxygen saturation (SmO₂ = O₂Hb/total Hb). Changes in cerebral blood volume (ΔCBV) after caffeine or aminophylline administration were calculated. Cerebral blood flow velocity (CBV) in the pericallosal artery was evaluated by cerebral Doppler ultrasounds. Results: Data collected by NIRS and cerebral Doppler ultrasounds did not show significant differences before and after caffeine treatment. We observed a significant increase in O₂Hb and HHb concentration and in CBV at 30 min after the infusion of aminophylline, which tended to return to baseline at the end of the study period. Conclusion: Caffeine does not significantly affect brain hemodynamics, while aminophylline induces a significant transient increase in O₂Hb and HHb concentration and CBV.

The effect of aminophylline on right heart function in young pigs after ligation of the right coronary artery.

An experimental model of right heart failure was developed to determine the effects of fluid loading and aminophylline on right heart function. We hypothesised that aminophylline would specifically improve right heart function through a decrease in pulmonary vascular resistance and, possibly, an increase in cardiac contractility. Right heart infarct was induced in ten experimental pigs and seven control pigs by ligating branches of the right coronary artery. The effect of fluid loading with a colloid solution and subsequent bolus doses of aminophylline on haemodynamics was observed. Fluid loading improved haemodynamics as expected. Aminophylline transiently improved cardiac index and pulmonary vascular resistance, but simultaneously caused an increase in heart rate and a decrease in stroke volume. Although aminophylline may reduce right heart afterload, it did not improve overall cardiac function in this experimental model of right heart infarction.

Effects of intravenous theophylline, aminophylline and ethylenediamine on antigen-induced bronchoconstriction in guinea pigs.

The antiasthmatic effect of i.v. injection of theophylline was compared with that of aminophylline by using an antigen-induced bronchoconstriction model in sensitized guinea pigs. Both theophylline and aminophylline showed dose-dependent inhibition of antigen-induced bronchoconstriction. Statistically significant differences were observed at theophylline doses of 20 and 40 mg/kg and at aminophylline doses of 25 and 50 mg/kg. Thus, antiasthmatic effects of both drugs appeared to be similar. In addition, intravenous ethylenediamine did not influence either airflow in normal guinea pigs or bronchoconstriction induced by antigen at doses up to 30 mg/kg. In conclusion, the ethylenediamine in aminophylline may not influence the antiasthmatic action of theophylline, and the therapeutic effects of theophylline and aminophylline are suggested to be similar.

Aminophylline in the treatment of fluid overload

Aminophylline has not been studied as an adjunct diuretic in critically ill children. Our purpose was to evaluate its use in the treatment of fluid overload in these patients. Open, controlled clinical trial. Pediatric intensive care unit. Study subjects ranged from 2-46 months of age, were fluid overloaded, and were receiving a continuous infusion of furosemide (> or =6 mg/kg/day). Patients with hemodynamic instability or liver dysfunction were excluded. A single dose of aminophylline (6 mg/kg) was given after establishing baseline values. There were no additional diuretics or changes in vasoactive agents during the study. Urine output, creatinine clearance, and sodium and potassium excretion were measured before and after administration of the aminophylline bolus. Heart rate and mean arterial pressure (mm Hg) were recorded hourly. Urine output increased by >80% (p < .01) during the first 2 hrs after administration of the aminophylline bolus and then returned to baseline by 4 to 6 hrs. The change in urine output is consistent with the pharmacokinetics of aminophylline. Heart rate and mean arterial pressure exhibited a change of <10% from baseline. These results suggest that aminophylline is an effective adjunct to furosemide in increasing diuresis in critically ill children with fluid overload. The increased diuresis can be accomplished without increased risk if drug levels are adequately monitored.

DIFFERENCE IN BRONCHOPROTECTIVE EFFECTS OF BRONCHODILATORS ON POSTALLERGIC PROPRANOLOL-INDUCED BRONCHOCONSTRICTION

Administration of propranolol provokes bronchoconstriction only in asthmatic patients. It is unknown whether bronchodilator therapy can prevent the propranolol-induced bronchoconstriction (PIB). We previously reported an animal model of PIB in which bronchoconstriction is caused by propranolol when inhaled 20 minutes after an antigen provocation in passively sensitized guinea pigs. Our goal was to evaluate the bronchoprotective effects of bronchodilators on the PIB in our animal model. Propranolol was inhaled 20 minutes after an antigen challenge in passively sensitized, anesthetized, and artifically ventilated guinea pigs. Atropine (5mg/kg) and equipotent doses of salbutamol (0.6ug/kg) and aminophylline (25mg/kg), which were determined by the dose-response curves for inhibition of histamine induced bronchoconstriction, were intravenously administered 5 minutes before the propranolol inhalation. Treatment of the animals with 25 mg/kg of aminophylline, but not with 0.6ug/kg of salbutamol or 5mg/kg of atropine, significantly prevented the PIB. These results show that our animal model is an experimental model of PIB which is resistant to beta2 -agonists or anticholinergics and suggest that amino-phylline may be useful to prevent and treat PIB resistant to beta2 -agonists.

Adenosine mediates spinal norepinephrine-produced antinociception as revealed by nociceptive discharges in parafascicular neurons in rats

The effects of intrathecal pretreatment with aminophylline on intrathecal norepinephrine-produced or serotonin-produced suppression of noxiously evoked discharges in thalamic parafascicular neurons were investigated in 35 urethane-anesthetized rats. The results showed that: (1) both intrathecal norepinephrine (15 nmol) or serotonin (20 nmol) produced significant suppression of noxiously evoked discharges in parafascicular neurons; (2) intrathecal aminophylline (120 nmol) blocked the norepinephrine-produced suppression of noxiously evoked discharges, while the same dose of aminophylline exhibited no significant effect on the serotonin-produced suppression of these discharges in parafascicular neurons. The results suggest that spinal norepinephrine-produced, but not serotonin-produced, antinociceptive effects may be mediated by adenosine as one of successive chemical links in the spinal dorsal horn circuitry.

Effects of high-dose ipratropium bromide and oral aminophylline on spirometry and exercise tolerance in COPD

Exercise tolerance in chronic obstructive pulmonary disease (COPD) patients treated with oral aminophylline may be different from those treated with high-dose inhaled ipratropium bromide. The purpose of this study was to compare the effects of therapeutic doses of oral aminophylline with high-dose ipratropium bromide on spirometry and exercise tolerance. The study was conducted on three consecutive days in a double-blind, randomized, crossover fashion. Baseline studies obtained on each study day included vital signs, simple spirometry and a symptom-limited maximal cardiopulmonary stress test, after which patients received one of the following treatments on each day: Treatment 1, inhaled ipratropium (total dose of 144 μg) with placebo tablets; Treatment 2, inhaled placebo with oral aminophylline (400 mg); Treatment 3, inhaled placebo and placebo tablets. Simple spirometry was repeated at 60 and 120 min after baseline. Vital signs and cardiopulmonary stress testing was repeated at 120 min. Eighteen patients were enrolled in the study, and 17 of these completed the study. There was a significant ( P<0·05) increase in both forced expiratory volume in 1 s (FEV 1), from 0·75 (0·21) to 0·92 (0·3), and forced vital capacity (FVC), from 1·8 (0·79) to 2·11 (0·84), with high-dose ipratropium despite prior β-agonist therapy. Lack of improvement in exercise capacity was noted with ipratropium despite improvement in spirometry. These results suggest that elderly patients with severe COPD may have exercise limitation that is not directly dependent on severity of airflow obstruction. Ipratropium bromide and aminophylline demonstrated no acute effects on exercise capacity.

Aminophylline and Doppler time-averaged mean velocity in the middle cerebral artery in preterm neonates.

The purpose of this study was to assess the effect of an intravenous loading dose of aminophylline (6 mg/kg) on Doppler time-averaged mean velocity in the middle cerebral artery in ventilated preterm neonates. Twenty infants were studied by colour/duplex Doppler technique prior to and at 5, 10, 30 and 60 min after the administration of aminophylline. Aminophylline treatment was associated with a statistically significant reduction in time-averaged mean velocity from baseline (P < 0.001) and an increase in heart rate (P < 0.001) at all timepoints. The largest reduction in time-averaged mean velocity of 19% (95% confidence interval -10 to -28%) occurred at 10 min post-dose. There were no statistically significant changes in transcutaneous PCO2 or mean arterial blood pressure. The observed reduction of 19% from baseline in time-averaged mean velocity following treatment with aminophylline alone is unlikely to be of clinical importance. Whether aminophylline in combination with other drugs that decrease central blood flow velocity such as indomethacin and/or dexamethasone could result in a clinically significant reduction deserves further study.

Effect of Aminophylline on High-energy Phosphate Metabolism and Fatigue in the Diaphragm

Diaphragmatic fatigue causes respiratory failure, for which aminophylline has been used as therapy. Because the mechanism of action of aminophylline in reversing diaphragmatic fatigue is unclear, we used in vivo 31P magnetic resonance spectroscopy (MRS) to determine the relation between diaphragmatic activation, force output, and aerobic metabolism. Bilateral phrenic stimulation was used to pace the diaphragm in pentobarbital-anesthetized piglets (6-10 weeks old; n = 44). Esophageal and abdominal pressures were measured to calculate transdiaphragmatic pressure (Pdi) (Pdi = abdominal pressure-esophageal pressure) as an index of force output. Activation was determined by the amplitude of the compound action potential of the diaphragmatic electromyogram. Aerobic metabolism was assessed with a 31P MRS surface coil on the right hemidiaphragm with the animal in a 4.7-T magnet. The animals were divided into four groups based on aminophylline loading dose: saline, aminophylline 10 mg/kg (A10), aminophylline 20 mg/kg (A20), and aminophylline 40 mg/kg (A40). After aminophylline loading the diaphragm was paced for 25 min followed by a 10-min recovery. Aminophylline concentrations were 12.2 +/- 0.7, 21.9 +/- 2.4, and 44.9 +/- 3.6 mg/l in the A10, A20, and A40 groups, respectively. Compound action potential amplitude decreased in all groups by 30% after 25 min of pacing. Conversely, Pdi remained at 100 +/- 3% of the initial value after 5 min of pacing in the A40 group but decreased to 75 +/- 3% in the saline group. Pdi recovered completely (103 +/- 17%) in the A40 group but remained depressed (72 +/- 6%) in the saline group. Pdi values were intermediate in the A10 and A20 groups. MRS data revealed inadequate energy supply/demand ratio in the saline group such that the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) increased to 1.01 +/- 0.09 after 5 min of pacing. Pi/PCr remained unchanged in the A40 group and was intermediate in the A10 and A20 groups. beta-Adenosine triphosphate and intracellular pH did not differ among groups or as a function of pacing. Diaphragmatic blood flow increased from a resting value of 35-60 to 300-410 ml.min-1 x 100 g-1 during pacing in all groups and was not affected by aminophylline dose. Aminophylline, in a dose-dependent fashion, delays the onset of fatigue and improves recovery from fatigue. Delayed fatigue is associated with improved aerobic metabolism as reflected in a low Pi/PCr ratio.

Anticonvulsant Effects of Intracerebroventricular Adenocard in Theophylline-Induced Seizures

Study objective: To evaluate the potential anticonvulsant effects of Adenocard in theophylline-induced seizures, we developed a rodent model of theophylline neurotoxicity with resultant convulsions. We used this model to investigate the actions of intracerebroventricular (ICV) Adenocard on seizure onset. Participants: Male Sprague-Dawley rats. Interventions: Surgical cannulation of the jugular veins of the rats was followed by stereotaxic placement of a catheter in the right lateral ventricle. The rats then received 15 μg (5 μL) ICV Adenocard or an equivalent. Ten seconds later, continuous infusion of IV aminophylline was begun at a rate of 75 mg/minute until the appearance of generalized convulsions with maximal hindlimb extension. Results: Compared with vehicle-injected controls, rats that received ICV Adenocard had a significant delay in mean time to seizure (162.1 seconds versus 107.4 seconds; P<.001). There was a corresponding increase in the weight-adjusted convulsant dose of aminophylline after the ICV administration of Adenocard (311.4 mg/kg versus 470.4 mg/kg; P<.003). Conclusion: Our data indicate that ICV Adenocard ameliorates theophylline-induced seizures. Potential anticonvulsant benefits of Adenocard and other adenosinergic compounds for victims of severe theophylline poisoning should be investigated further. [Shannon M, Maher T: Anticonvulsant effects of intracerebroventricular Adenocard in theophylline-induced seizures. Ann Emerg Med July 1995;26:65-68.]

Changes in phrenic, hypoglossal and recurrent laryngeal nerve activities after intravenous infusions of aminophylline in cats

Aminophylline is known to have respiratory stimulant properties, and it has been suggested that it may also be effective in sleep apnoea. However, its role in this disorder remains uncertain. Theoretically, increasing upper airway motoneural activity in order to maintain airway patency might alleviate obstructive sleep apnoea. On the other hand, increasing the respiratory drive may also prove beneficial in treating central sleep apnoea. In these studies, we attempted to determine the effect of aminophylline on neural activities of the upper airway and diaphragm. We administered intravenously either a low dose (4 mg.kg-1) or a high dose (16 mg.kg-1) of aminophylline to decerebrated, vagotomized and paralysed cats, and continuously recorded the phrenic hypoglossal and recurrent laryngeal nerve activities for 3 h. Results showed that a high dose of aminophylline induced a marked increase in phrenic nerve activity, but not hypoglossal or recurrent laryngeal nerve activity. In a group treated with a low dosage of aminophylline, a significant increase of activity was found in all three nerves. Furthermore, phrenic nerve activity increased more with a high dose than with a low dose. We confirmed that aminophylline has dose-dependent and selective effects on respiratory neural activity. A low dose acts on the upper airway and diaphragm, but a high dose induces a marked increase in central respiratory drive. According to our results, low dose aminophylline might be beneficial in obstructive sleep apnoea, whereas, a high or low dose might improve some cases of central sleep apnoea.

Profound shock resulting from a large dose of dipyridamole

Acute ingestion of more than 200 mg dipyridamole may result in minor symptoms. The reported highest dosage of acute ingestion was 1250 mg. Most experiences of acute ingestion come from dipyridamole thallium image, oral application of 300–400 mg or intravenous 0.56 mg/kg. The systemic or cardiovascular complication could be rapidly reversed by intravenous use of aminophylline, 50–240 mg. We report an experience in dealing with the highest ever dose, 1750 mg, of dipyridamole overdose by usual dose of aminophylline.

Aminophylline exhibits convulsant action in rats during ontogenesis

Aminophylline-induced seizures were studied in 166 male albino rats in five age groups — 7, 12, 18, 25 and 90 days old. Aminophylline injected in doses from 150–350 mg/kg i.p. elicited both minimal, clonic and major, i.e. generalized tonic-clonic seizures during the 60-min observation period. The pattern of minimal seizures did not change during development; major seizures exhibited changes in proportion to their three phases — running, tonic and clonic phases. Dependence on the dose of aminophylline was observed in the incidence of major seizures as well as in shortening of latencies of both types of seizures. More marked convulsant effects of aminophylline in 7-, 12- and 18-day-old rat pups than in older animals might be due to pharmacokinetic as well as pharmacodynamic factors.

Adequacy of recommended aminophylline loading doses in children

The adequacy of a loading dose of aminophylline 6 mg/kg i.v. in hospitalized pediatric patients with reactive airway disease was studied. Children six months to 14 years of age were studied to determine their serum theophylline concentrations after they were given an aminophylline loading dose of 5-7 mg/kg i.v. and to see whether they had to receive additional bolus doses. Bolus doses were infused over 20-30 minutes and were followed by a continuous infusion. Additional bolus doses were administered if the patient's serum theophylline concentration and clinical condition indicated they were necessary. Data from two separate phases of the study were combined for analysis. Phase 1 was designed for estimating population pharmacokinetic values. Some 72% of the 64 patients studied had subtherapeutic serum theophylline concentrations (< 10 mg/L) within 5.5 hours of the loading dose, and 78% required at least one additional bolus dose. Males had significantly lower serum theophylline concentrations than females; of the patients with subtherapeutic concentrations, 67% were males. Patients five years of age or younger were more likely than older children to have subtherapeutic theophylline concentrations. A 6-mg/kg loading dose of i.v. aminophylline did not produce adequate serum theophylline concentrations or eliminate the need for a second bolus dose in most pediatric patients with acute exacerbations of asthma.

Aminophylline partially blocks ventilatory depression with hypoxia in the awake cat

In humans and cats, the ventilatory response to 30 min of moderate hypoxia is biphasic, an initial increase being followed by a decrease in ventilation to levels that are often less than halfway between the initial response and the air-breathing control level. The decrease, or hypoxic depression, is thought to be of central origin. In humans, intravenous aminophylline, an adenosine blocker, blunts hypoxic depression and may completely block it in anesthetized cats. We studied 11 adult cats while awake, measuring ventilation and end-tidal Po2 (Peto2) and Pco2 (Petco2) during 30 min of isocapnic hypoxia (Petco2 32 Torr (1 Torr = 133.3 Pa), Peto2 60 Torr) after intravenous aminophylline on 1 day and saline on another. On the saline day hypoxia initially produced a 75% increase in ventilation, which declined at 30 min to 110% of control, largely owing to a decrease in tidal volume. With aminophylline, room-air ventilation was slightly increased, and hypoxia initially produced a 50% increase in ventilation, which then declined to 130% of control at 30 min. Late in hypoxia, ventilation was significantly greater with aminophylline than with saline. The degree of hypoxic depression was not related to blood theophylline levels and was similar after aminophylline doses of 10 and 13 mg/kg. We conclude that hypoxic depression is at least partially due to adenosine accumulation, the effect of aminophylline being likely due to central adenosine blockade.

Theophylline Disposition in Korean Patients with Congestive Heart Failure

This study proposed to determine the systemic disposition of theophylline in Korean adult patients during decompensated congestive heart failure compared with disposition after recovery. An experimental, prospective, self-controlled, nonrandomized design was used. The study was performed in a general community hospital located in Pusan, Korea. Eight nonsmoking elderly Korean patients with decompensated congestive heart failure presenting to the emergency department were included in the study. Consecutive patients who met entrance criteria were selected. All patients completed the study. A single dose of aminophylline 6 mg/kg was administered by intravenous infusion over 30 minutes. Standard methods of congestive heart failure therapy were used in each patient, including bed rest, restriction of sodium, and drug therapy including digoxin. After compensation of congestive heart failure was achieved, the theophylline infusion was repeated. Serum theophylline concentrations were measured at 2, 6, 12, and 18 hours after completion of the dose at baseline and following treatment. A clinically and statistically significant improvement in mean theophylline total body clearance was demonstrated following treatment (from 21.7 +/- 2.8 to 43.4 +/- 4.7 mL/kg/h [mean +/- SEM]; p < 0.01). Comparison of these results with a computer model based on literature averages of peoples of all nationalities showed significant underprediction of theophylline clearance both before (p < 0.05) and after (p < 0.01) treatment. The theophylline elimination half-life prior to treatment was 18.2 +/- 2.2 hours and decreased to 9.1 +/- 0.8 hours following treatment (p < 0.01). There was no statistical difference between the computer-model predicted initial theophylline half-life and the measured value, but the model significantly underpredicted the improvement following treatment. The improvement in theophylline clearance demonstrated in this study appears to be greater than that reported for Western patients. This has practical application to the calculation of appropriate theophylline maintenance dosage regimens in Korean patients with cardiac failure. These data support the need for consideration of racial differences in individualizing dosage regimens. We suggest that all kinetic models, whether software supported or not, should consider incorporating ethnic origin as a demographic factor that helps select the proper model for individual patients.

Evaluation of New Patient-Side Immunoassay System (Biotrack Theophylline) for Determination of Theophylline in Blood.

A new patient-side immunoassay system, Biotrack Theophylline®, was evaluated and compared with the widely-used monitoring analysis methods, enzyme-multiplied immunoassay (EMIT®) and fluorescence polarization immunoassay (TDx®). Blood samples were obtained from five healthy subjects who received oral multiple doses of aminophylline for three days. The theophylline concentrations obtained by Biotrack Theophylline correlated well with those by EMIT (r=0.974) and TDx (r=0.982), respectively. A good correlation was also observed between EMIT and TDx (r=0.986). The mean (±2standard deviation) discrepancy between two methods was as follows: EMIT-Biotrack: -0.23±14.93μmol/L, TDx-Biotrack: -4.83±11.96μmol/L, TDx-EMIT: -4.52±15.01μmol/L. These results indicate that Biotrack Theophylline is a reliable method for the therapeutic monitoring of theophylline by immediate determination of the drug concentration.