• 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.

• YAKHAK HOEJI
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• v.33 no.1
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• pp.10-14
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• 1989

As potential xanthine bronchodilators related to Doxofylline (1b), 2-(7-theophyllineethyl)-1,3-dioxolane (3), 7-(3,3-dimethoxypropyl) theophylline(5), 2-methyl, 2-(7-theophyllinemethyl)-1,3- dioxolane (8a), 2-phenyl, 2-(7-theophyllinemethyl)-1,3-dioxolane (8b) and 2-(7-theophyllinemethyl)-1,3-benzodioxolane(14) were synthesized from theophylline (1a).

• Archives of Pharmacal Research
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• v.20 no.4
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• pp.318-323
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• 1997

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethyinitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life $(t_{1/2})$ in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL $(8.67{\pm}4.85%)$ decreased about four-folds, but in DMNA $(73.00{\pm}9.85%)$ similar result war observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.

• 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.

• Korean Journal of Clinical Pharmacy
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• v.29 no.2
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• pp.115-124
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• 2019

The purpose of this systematic review and meta-analysis was to assess the preventive effect of theophylline on acute kidney injury and the ameliorative effect of theophylline on renal function in asphyxiated neonates. A literature search of the PubMed/Medline, Embase, and Cochrane Library databases for information published up to February 2019 was conducted. All studies that reported the incidence rate of acute kidney injury, serum creatinine level, and glomerular filtration rate after the randomized administration of theophylline or placebo were included. In total, eight studies involving 498 neonates were eligible. The incidence rate of acute kidney injury was significantly lower in the theophylline group than in the placebo group (risk ratio [RR]: 0.42, 95% confidence interval [CI]: 0.32-0.55, p < 0.001). The changes in serum creatinine level in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 and 5 days of age (weighted mean difference [WMD]: -0.51, 95% CI: -0.62 to -0.40, p < 0.001, and WMD: -0.26, 95% CI: -0.34 to -0.18, p < 0.001, respectively). The changes in glomerular filtration rate in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 days of age and the last day of follow-up (WMD: 12.30, 95% CI: 9.39-15.21, p < 0.001, and WMD: 9.35, 95% CI: 6.43-12.27, p < 0.001, respectively). These results suggested that theophylline has a beneficial effect on the prevention of acute kidney injury in neonates with perinatal asphyxia.

• 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.

• The Korean Journal of Zoology
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• v.18 no.1
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• pp.27-40
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• 1975

dbcAMP와 theophylline이 난자의 성숙을 억제하는 기작과 난자내 glycogen 함량과의 관계를 밝혀보기 위하여 실험한 결과는 다음과 같다. 1. 생쥐 여포난자의 PAS 양성물빌은 glycogen이며 핵의 성숙분열이 진행됨에 따라 glycogen의 함량은 감소한다. 2. dbcAMP나 theophylline에 의해 핵의 성숙이 억제된다 하더라도 난자내의 glycogenolysiss는 촉진된다. 이에 반해 핵분열이 일어나지 않은 난자는 배양이 진행되더라도 glycogen을 그대로 유지하고 있다. 일단 dbcAMP나 theophylline에 의해 성숙이 억제되었던 난자가 성숙과정에 들어가려면 다시 glyconeogenesis가 일어나 세포질내의 glycogen의 양이 회복하며 이때의 glycogen은 핵성숙과 더불어 소모된다. 3. Glycogen의 회복은 배양액내의 glucose 유무에 관계없이 이루어지며 따라서 이는 난자내 glucose 혹은 다른 전구물질에 의해 이루어지리라고 추측된다. 4. 결국 dbcAMP나 theophylline은 난자내 cAMP의 양을 증가시켜 glycogen의 소모를 일으키는 것으로 생각되며, glycogenolysis와 난자의 핵 성숙과정이 별개로 진행되기는 하지만 성숙의 요건은 일정량 이상의 glycogen이 함유되어 있어야 한다는 것을 알게되었다.

• 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.

• Journal of Embryo Transfer
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• v.15 no.1
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• pp.95-102
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• 2000

Techniques for manipulation of spermatozoa and oocytes have been widely used for in vitro production(IVP) of Hanwoo. This study was conducted to examine the effects of theophylline and heparin on frozen-thawed Hanwoo sperm for enhancing the efficiency of IVP technique. Oocytes were inseminated with forzen bull semen treated with either theophylline or heparin for examining the effect of each substance on fertilization and subsequent development. More (P<0.05) oocytes formed pronucleus and develop to the morula and blastocyst stages after inseminated with sperm treated with heparin than after inseminated with sperm treated with theophylline. The pregnancy rate after embryo transfer was higher after heparin treatment than after theophylline treatment, but did not differ significantly. There was no significant difference of offspring delivery between two groups. In conculsion, theophylline and heparin can be used for enhancing the efficiency of IVP system for Hanwoo. Considering characteristics of these substance, theophylline may be useful in the artificial insemination system, which requires vigorous sperm motility. While, heparin supporting sperm viability in vitro can be effectively used for improving in vitro-fertilization system.

• Polymer(Korea)
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• v.32 no.2
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• pp.138-142
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• 2008

Molecularly imprinting technology is an effective method to prepare a synthetic material with a high selectivity to a target molecule. In this study, a molecularly imprinted polymer (MIP) was synthesized via UV-polymerization using theophylline and UV-curable polyester-acrylate resin as a template molecule and a crosslinker, respectively. To elucidate the effects of functional monomer type on the performance of the MIP, each MIP was synthesized using mathacrylic acid, acrylic acid, and acryl amide as functional monomers. Each MIP showed higher rebinding capacity to theophylline than its corresponding non-imprinted polymer (NIP). The MIP synthesized using mathacrylic acid as a functional monomer showed the highest rebinding capacity to theophylline. The selectivity of the MIP was investigated using a solution with caffeine having a very similar structure to theophylline. The binding performance of the MIP to theophylline decreased when distilled water was used as a solvent, which has more polarity than chloroform.