To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.
Administration, Oral ; Animals ; Arylamine N-Acetyltransferase ; genetics ; metabolism ; Caffeine ; metabolism ; urine ; Cytochrome P-450 CYP1A2 ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Male ; Medicine, Tibetan Traditional ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Theophylline ; urine ; Uracil ; analogs & derivatives ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.
Administration, Oral ; Asian Continental Ancestry Group ; Calibration ; Chromatography, Liquid ; Delayed-Action Preparations ; metabolism ; Healthy Volunteers ; Humans ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry ; Theophylline ; metabolism ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

Pure and drug hydrophilic matrix tablets were prepared by direct compression method with theophylline as a model drug. The characteristics of four hydrophilic matrix polymers, hydroxypropylmethylcellulose (HPMC), polyethylene oxide (PEO), sodium alginate (NaAlg) and xanthan gum (XG), were compared by investigating the water absorption, swelling, erosion and gel layer strength. The sequence of water absorption rate was XG > NaAlg (H) > PEO > NaAlg (L) > HPMC; The sequence of swelling index was XG > PEO > HPMC > NaAlg; The sequence of erosion rate was NaAlg (L) > NaAlg (H) > PEO80 > PEO200 > PEO300 > XG approximately PEO400 approximately K4M > K15M > PEO600 approximately K100M; The sequence of the gel layer strength was PEO > HPMC > XG > NaAlg. For the PEO and HPMC matrix tablets, with the polymer molecular weight increased, the drug release mechanism was gradually transferred from mainly depending on the erosion to the diffusion; for SAL matrix tablets, the drug release mainly depends on erosion mechanism; and for XG matrix tablets, the drug release mainly depends on non-Fick diffusion mechanism. Comparison of the performance difference between the polymer materials will contribute to rational design and prediction of drug release behaviors from matrix tables and ultimately to achieve clinical needs.
Alginates ; chemistry ; Bronchodilator Agents ; administration & dosage ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Excipients ; chemistry ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Hypromellose Derivatives ; Methylcellulose ; analogs & derivatives ; chemistry ; Molecular Weight ; Polyethylene Glycols ; chemistry ; Polymers ; chemistry ; Polysaccharides, Bacterial ; chemistry ; Tablets ; Theophylline ; administration & dosage ; Water

PURPOSE: Low-dose theophylline has anti-inflammatory effects. The aim of this study was to evaluate the effects of adding theophylline compared with increasing the dose of inhaled corticosteroid (ICS) on symptomatic asthma. MATERIALS AND METHODS: The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. The extracted data were further analyzed by a meta-analysis RESULTS: Four randomized, controlled, parallel studies were selected. Addition of theophylline produced a greater increase of forced expiratory volume in one second as %predicted (FEV1pred) by 2.49% [95% confidence interval (CI) 1.99-3.00; z = 9.70; p < 0.001], compared with increasing the dose of ICS. There was no difference between the two treatments in terms of peak expiratory flow (PEF). CONCLUSION: Addition of theophylline to ICS has similar therapeutic effects on improving lung function as increasing the dose of ICS in the treatment of symptomatic asthma.
Adrenal Cortex Hormones/administration & dosage/*therapeutic use ; Anti-Asthmatic Agents/administration & dosage/*therapeutic use ; Asthma/*drug therapy ; Forced Expiratory Volume/drug effects ; Humans ; Randomized Controlled Trials as Topic ; Theophylline/*therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the effect of traditional Chinese medicine preparations on bronchial hyperesponsiness (BHR)-induced cough.

METHODSixty patients with cough due to BHR (shown by positive bronchial provocation test) were randomly divided into Chinese medicine group (n = 30) and control group (n = 30) to receive Bufeishenqingre decoction twice a day and 100 mg theophylline sustained-release capsules twice a day for one month, respectively. The changes of the clinical symptoms were observed during the treatment and bronchial infrared imaging was performed before and after the treatment.

RESULTSThe symptoms of patients in the Chinese medicine group were more effectively alleviated than those of the control group (P < 0.05). The difference in the temperature between the bronchial lesions and the surrounding normal mucosa changed more obviously in the Chinese medicine group (P < 0.01).

CONCLUSIONBufeishenqingre decoction can relieve the symptoms and improve the abnormalities in infrared imaging of patients with BHR-induced cough.

Adult ; Bronchial Hyperreactivity ; complications ; drug therapy ; Bronchial Provocation Tests ; Bronchodilator Agents ; administration & dosage ; Cough ; drug therapy ; etiology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Theophylline ; administration & dosage ; Young Adult

Administration, Inhalation ; Adrenal Cortex Hormones ; pharmacology ; Asthma ; drug therapy ; metabolism ; Child ; Child, Preschool ; Drug Interactions ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Male ; Theophylline ; pharmacokinetics ; pharmacology ; Treatment Outcome

OBJECTIVETo observe the role of theophylline in relieving airway symptoms and inflammation in patients with mild asthma.

METHODSFifty-six patients with mild asthma were randomly divided into treatment group (n=41) receiving oral theophylline at daily dose of 4 to 6 mg/kg for 16 weeks and control group (15 cases) without medication other than beta2 antagonist, which was administered when necessary in both groups. Peripheral blood T-lymphocyte subsets (CD3(+), CD4(+), and CD8(+)) and pulmonary function (PEF(am) and PD(20)) before and at 8 and 16 weeks during treatment were measured.

RESULTSSignificant difference was observed in CD3+ and CD4(+) T-lymphocyte subsets after medication with theophylline (P<0.05) in the patients, and PEF(am) and PD(20) were also significantly different from those of the control group (P<0.05). Theophylline significantly improved the clinical symptom scores (P<0.05) and decreased the asthma attacks.

CONCLUSIONLow-dose oral theophylline may significantly relieving airway inflammation in patients with mild asthma.

Administration, Oral ; Adult ; Asthma ; drug therapy ; immunology ; physiopathology ; Bronchodilator Agents ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Respiratory Function Tests ; T-Lymphocyte Subsets ; drug effects ; immunology ; Theophylline ; administration & dosage ; therapeutic use ; Treatment Outcome

AIMTo investigate the in vitro influencing factors on drug release from matrices with sodium alginate as the hydrophilic polymer.

METHODSSodium alginate hydrophilic matrix tablets were prepared by direct compression method with theopylline as a model drug. The in vitro influencing factors on drug release behavior from matrices were studied by investigating the swelling, water uptake and erosion characteristics of pure sodium alginate matrices.

RESULTSThe results showed that drug release rate and drug release mechanism were both related to the viscosity of sodium alginate used in matrices, pH values and ionic strength of dissolution media and rotation speeds.

CONCLUSIONSodium alginate can be tailor-made to suit the demands of applicants in sustained delivery systems as a good candidate of hydrophilic polymer.

Alginates ; administration & dosage ; chemistry ; Chemistry, Pharmaceutical ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Glucuronic Acid ; administration & dosage ; chemistry ; Hexuronic Acids ; administration & dosage ; chemistry ; Hydrogen-Ion Concentration ; Solubility ; Tablets ; Theophylline ; administration & dosage ; chemistry ; Viscosity

Acute Disease ; Asthma ; drug therapy ; Bronchodilator Agents ; administration & dosage ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infusions, Intravenous ; Male ; Theophylline ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome

Metabolic and electrolyte abnormalities, including hypokalemia, hyperglycemia and lactic acidosis, are associated with theophylline overdose. However, we report an unusual case of sinus tachycardia, lactic acidosis, hypokalemia and hyperglycemia associated with the usual theophylline dose in a patient with asthma. The theophylline dose was 200 mg orally twice daily. Three hours after administration of the third dose, the patient experienced palpitation. An electrocardiogram showed a sinus tachycardia. Arterial blood gas analysis revealed a mixed metabolic acidosis and respiratory alkalosis. Serum lactate level was 51 mmol/L (normal 0.7~2.1 mmol/L). Biochemistry results were sodium 136 mEq/L, chloride 99 mEq/L, potassium 1.9 mEq/L and glucose 204 mg/dL. Our case suggests that a possibility of theophylline-associated metabolic abnormalities should be considered when an asthmatic patient given the usual theophylline dose presents with lactic acidosis, hypokalemia and hyperglycemia of unknown etiology.
Acidosis, Lactic/*chemically induced ; Adult ; Asthma/drug therapy ; Bronchodilator Agents/administration & dosage/*adverse effects ; Case Report ; Female ; Human ; Hyperglycemia/chemically induced ; Hypokalemia/etiology ; Tachycardia, Sinus/chemically induced ; Theophylline/administration & dosage/*adverse effects