• Korean Journal of Clinical Pharmacy
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• v.10 no.3
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• pp.107-110
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• 2000

Theophylline and $\beta$-adrenergic agonists are frequently used together in patients with respiratory diseases. However the clinical impact of $\beta_2$-adrenergic agonists on the blood concentration of theophylline is not fully evaluated. Formoterol, a newly available oral ${\beta}_2$-adrenergic agonist is frequently used in pediatric respiratory patients. The objective of this study was to investigate the effect of oral formoterol on theophylline's blood concentration. Randomized prospective study was conducted. Twenty-four children were enrolled on the study. Their age ranged 2 to 73 months (mean 35.8 months). Theophylline group (12 patients) received 10 mg/kg/day of for theophylline orally. Theophylline/formoterol group (12 patients) received 10 mg/kg/day of theophylline and $4\;{\mu}g/kg/day$ of formoterol orally. All medications were administered at least for 5 days starting on admission day. Theophylline's trough concentrations were obtained on days 3 and day 5. Pulse rates were recorded before the study medications were given on admission, and days 3 and day 5. Statistical significance was calculated by two-tailed Student's t-test. Theophylline's levels in children given theophylline and formoterol together were lower an those given theophylline alone ($6.38\pm0.90\;{\mu}g/ml\;vs\;7.43\pm0.77\;{\mu}g/ml$ on day 3(p<0.05), $5.62\pm0.56\;{\mu}g/ml\;vs.\;6.78\pm0.61\;{\mu}g/ml$ on day 5 (p<0.05)). In both groups, theophylline's trough concentration on day 5 were lower than day 3. There was no significant side effects in both groups. In conclusion, the new ${\beta}_2$ selective adrenergic agonist formoterol reduced serum theophylline levels in children with respiratory diseases. Further investigation is needed to clarify the long term effect of this drug interaction.

• Korean Journal of Clinical Pharmacy
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• v.2 no.1
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• pp.23-28
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• 1992

This study was attempted to investigate the pharmacokinetics of theophylline(4mg/kg) in the rabbits of carbon tetrachloride induced hepatic Cailure, The plasma concentration and relative bioavailability of theophylline were increased significantly in hepatic railure rabbits compared with those of normal rabbits. There was significant relationship between SGOT value and bioavailability parameters of theophylline. From the results of this experiments, dosage regimen of theophylline is considered to be adjusted in dose size and dosing interval using SGOT values.

• KSBB Journal
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• v.17 no.2
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• pp.207-211
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• 2002

The theophylline imprinted membrane was prepared by a wet phase inversion method. Theophylline was implanted during copolymerization of acrylonitrile with acrylic acid or implanted in the dimethyl sulfoxide solution containing10 wt% copolymer, p(AN-co-AA). Rolling the glass plate, on which the copolymer solution was cast, in water removed the sponge layer and thus made the membrane symmetric. The adsorption selectivity of the membrane toward template molecule was increased with the coagulation temperature of the membrane and the initial concentration of the theophylline and caffeine mixture.

• Toxicological Research
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• v.4 no.1
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• pp.1-12
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• 1988

In order to evaluate the effect of cigarette smoking on the pharmacokinetics of theophylline in Koreans, doses of 4.5 to 5.0 mg/kg of theophylline, as injectable aminophylline, were administered to 12 normal young volunteers (male, 22 to 35 yrs;mean, 26 yrs) through intravenous infusion over 30 minutes, and pharmacokinetics of theophylline were tested. Among subjects, six were nonsmokers and the other were smokers (range 1 to 2 packs/day). Also the correlations between plasma and saliva theophylline concentrations were investigated by determining the concentrations of theophylline in saliva simultaneously at each plasma sampling time. The total body clearances of theophylline in smokers (Mean${\pm}$SD, 0.0578${\pm}$0.0092 L/hr/kg)were appreciably higher than thoxe of nonsmokers (Mean${\pm}$SD, 0.0359${\pm}$0.0063 L/hr/kg), and the half-lives of theophylline in smokers averaged 5.36${\pm}$1.22hr, and significantly shorter than those of nonsmokers which averaged 9.14${\pm}$1.73hrs(p<0.005). But the apparent volumes of distribution of theophylline did not show any significant difference between smokers (Mean${\pm}$SD,0.44 ${\pm}$0.05L/kg) and nonsmokers (Mean${\pm}$SD, 0.46${\pm}$0.05L/kg). The average concentration ratios in saliva and plasma were 0.61 in smokers and 0.56 in nonsmokers after 2 hrs following drug administrations, and the smoker group had a slightly higher value of ratio(S/P) than the nonsmoker group (p<0.05). The correlations between saliva and plasma theophylline concentration in smokers were r=0.852(p<0.0005) within 2 hr and r=0.985(p<0.0005) after 2 hrs and also those of nonsmokers were r=0.729(p<0.0005) within 2 hrs and r=0.957(p<0.0005) after 2 hrs starting the infusion. From the results, it was found that smoking cigarettes had significantly increased the clearance of theophylline and that the relationships between saliva and plasma theophylline concentrations in all subjects were better after 2 hrs than within 2 hrs starting the infusion of aminophlline.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.379-383
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• 1991

This study was attempted to investgate the pharmacokinetics of theophylline (4 mg/kg i.v) in the rabbits pretreated with propranolol (1 and 2.5 mg/kg/hr, infusion) for four hours. The plasma concentration and AUC of theophylline were increased in rabbits pretreated with propranolol as compared with those of normal rabbits. The amount of cumulative urinary excretion and renal clearance and total body clearance were decreased in rabbits pretreated with propranolol as compared with those of normal rabbits. The apparent volume of distribution was slightly affected by change of the clearance of theophylline. From the results of this experiment, it is desirable that dosage regimen of theophylline should be adjusted when theophylline combined with propranolol in clinical pharmacy practice.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.546-552
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• 1998

Background: Up to 90% of a theophylline dose is biotransformed, by interaction with one or more the variants of the cytochrome P-450 drug metabolism system. Macrolides affect the elimination of theophylline by influencing on the microsomal enzyme systems. We evaluate the effect of erythromycin and new macrolides on the serum theophylline level and clearance. Method : Subjects consisted of moderate asthmatic patients with normal renal and hepatic functions. All subjects were non-smokers and treated with oral theophylline 400 mg per day. We randomly assigned 53 patients into four groups. Each group was treated with one macrolides, the first group erythromycin(n:19, 500 mg bid), second roxithromycin (n:14. 150 mg bid), third clarithromycin (n:10, 250 mg bid) and fourth azithromycin(n:10, 250 mg bid). We measured the serum theophylline level and clearance at three intervals, at pretreatment, after the first and fourth week after receiving the following macrolides, erythromycin, roxithromycin and clarithromycin. When azithromycin was administered, the serum theophylline level was measured at pretreatment and after one week of treatment They were measured by a computerized program of Bayesian method. Results : When compared with control, erythromycin and roxithromycin-treated groups had a significantly elevated serum theophylline level and decreased clearance. However, there were no significant changes of the serum theophylline level and clearance in clarithromycin and azithromycin-treated groups. Conclusion : These results suggest that theophylline dose may need to be readjusted and have periodic drug monitoring when erythromycin or roxithromycin is administered concurrently.

• Journal of Pharmaceutical Investigation
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• v.19 no.4
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• pp.191-194
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• 1989

Bioequivalence test of $Asthcontin^{\circledR}$ tablet, a commercial slow-release theophylline (TP) dosage form, was performed using $Slo-bid^{\circledR}$ capsule as the reference. Since it has been confirmed that the saliva concentration of TP is closely correlated with the plasma concentration in man, the area under the saliva concentration-time curve was used as a bioavailability parameter. The statistical analysis showed that the two dosage forms are equivalent in bioavailability estimating from the saliva concentration. The results supported that the use of soliva as a test sample provides simple and easy techniques for bioequivalence tests of TP-containing dosage forms.

• Korean Journal of Clinical Pharmacy
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• v.9 no.1
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• pp.55-61
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• 1999

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride treatment when aminophylline (8 mg/kg as theophylline, i.v.) was injected. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes was determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to $17\%$ of the control value while AUC (area under the plasma concentration-time curve) and $(t_{1/2})_{\beta}$ were increased to about 6 fold and 10 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to $33-41\%$ of the control value in microsomes of cirrhotic rat liver. From these results, it can be concluded that in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride the total body clearance of theophylline is markedly reduced due to a reduced hepatic metabolism.

• YAKHAK HOEJI
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• v.36 no.4
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• pp.321-325
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• 1992

Pharmacokinetic interaction of theophylline with pefloxacin following i.v. administrations was investigated in rabbits. Pefloxacin was coadministrated at doses of 10 and 20 mg/kg or previously administered for 6 days 10 and 20 mg/kg. Plasma concentration and AUC of theophylline were increased significantly (p<0.05) and the renal clearance $(CL_r)$, total body clearance $(CL_r)$ and the volume of distribution $(Vd_{ss})$ were decreased significantly (p<0.005) by the pretreatment. It demonstrates that adjustment of dosage regimen of theophylline should be considered when concomitant administration of pefloxacin is prescribed.

• Polymer(Korea)
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• v.31 no.2
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• pp.153-159
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• 2007

Biodegradable molecularly imprinted polymers (MIPs) can be applied in the biomedical area of biosensors, drug delivery, etc. Therefore, in this study, biodegradable theophylline MIPs were synthesized via photopolymerization using a poly $(\varepsilon-caprolactone)$ (PCL) macromer as a cross-linker and their physical properties were investigated. The yield for the synthesis of the PCL macromer with terminal acrylate groups was ca. 78 mol%. The products were characterized by the combination of FT-IR and $^1H-NMR$ spectroscopic analyses. UV/Visible spectroscopic analysis for removing and rebinding theophylline was performed by monitoring the theophylline concentration in the solution. In vitro biodegradation tests of the theophylline MIPs performed in phosphate buffered saline (PBS) solution at $37^{\circ}C$ showed good biodegradability of the MIPs.