OBJECTIVETo investigate the correlation of skin electric resistance changes with the blood drug content in acupoint transdermal administration, and to establish an new evaluation index for drug delivery efficiency through acupoints.

METHODSTwenty-four rabbits were randomly divided into an observation group and a control group. In the observation group, aminophylline was administrated through "Feishu" (BL 13), "Geshu" (BL 17) and "Danzhong" (CV 17) which are commonly used for treatment of bronchial asthma, and the control group through sham-points on the back. The skin resistance and plasma aminophylline content were determined after application of aminophylline to the points, and their changes with time were observed. The ratio of Css/Rss at stability was defined as delivery coefficient (DC) which reflects the efficiency of delivering drug at acupoints and sham acupoints.

RESULTSBoth the plasma aminophylline and the skin resistance value tended to steady about 6-8 h after application of aminophyiophylline. The DC in the acupoints was higher than that in the sham-acupoints (P < 0.01). And there was significant difference as DC of the "Feishu"was significant difference (BL 13) and "Danzhongas DC of the "Feish" (BLCV 17) compared with that of "Geshu" (BL 17) (P < 0.01).

CONCLUSIONThe bigger the DC is, the higher the efficiency of drug delivery is; the efficiency of drug delivery through acupoints is higher than that through sham-acupoints.

Acupuncture Points ; Administration, Cutaneous ; Aminophylline ; administration & dosage ; pharmacokinetics ; Animals ; Electric Impedance ; Female ; Male ; Rabbits

BACKGROUNDA patented remote controlled capsule (RCC) has recently been developed to provide noninvasive drug delivery to selected sites in the human gut that allows assessment of regional gastrointestinal (GI) drug absorption under a normal physiological environment. The objective of this study was to investigate the rate and extent of aminophylline absorption after site-specific delivery of the drug in the GI tract using RCC and a magnetic marker monitoring (MMM) technique.

METHODSThis study was conducted in twelve healthy male subjects, in a three-treatment, randomized, crossover manner with a 7-day washout. Eligible subjects received a 150 mg aminophylline dose through an oral administration, or via a remote controlled capsule, delivered to the small bowel or ascending colon. MMM was employed to monitor the GI transit of the RCC, and the radio-frequency signal was used to activate capsules at target sites. Blood samples were obtained at regular intervals until 24 hours post dose/activation. Plasma theophylline concentrations were measured by a TDx System Analyzer. A comparison of the PK profile with the oral dosing route of aminophylline was performed after delivery to the small bowel and colon.

RESULTSThe RCC was well tolerated in volunteers. The mean capsule activation time for the small bowel and ascending colon was 2.07 hours and 6.08 hours post dose. Aminophylline had similar absorption profiles from the small bowel compared with the stomach, with an area under the curve (AUC(t)) ratio of 92% vs. the stomach, but a lower absorption profile from the ascending colon, with an AUC(t) ratio of 47.2% vs. the stomach.

CONCLUSIONSThe proprietary of the RCC and MMM technique offer the opportunity to obtain data on the intestinal absorption of a drug in humans under noninvasive conditions. Aminophylline is rapidly and efficiently absorbed from the small bowel. While colonic absorption was limited by the poor water condition although effective absorption was observed from the ascending colon. This provides an opportunity for rational development of modified-release formulations as well as alternative dosage forms.

Adult ; Aminophylline ; administration & dosage ; pharmacokinetics ; Capsules ; administration & dosage ; pharmacokinetics ; Colon ; metabolism ; Humans ; Intestine, Small ; metabolism ; Male ; Young Adult

PURPOSE: To determine if intravenous aminophylline adds any efficacy to nebulized albuterol and intravenously administered corticosteroid in children who hospitalized with mild to moderate asthma. METHOD: Subjects were children between the ages of 5 and 15 years admitted of acute asthma attack to Department of Pediatrics, Kyung Hee University Hospital. All patient received therapy with albuterol delivered with nebulization at 4-6 hour interval and intravenously adminstered methylprednisolone in standardized doses. Thirty patients were recruited to receive either an intravenous aminophylline(n=15) or not(n=15). The outcome variables were:duration of hospitalization, percent of predicted peak expiratory flow rates recorded at 12-hour intervals and side effects. When intravenously administered medications were discontinued, therapy continued with oral administration of theophylline. Twice daily assessments of clinical asthma symptoms were made by using a scoring system consisting of respiratory rate, wheeze and accessory muscle use. RESULTS: 1) There were no significant differences at study entry in age, sex, race, number of previous hospital admission, clinical symptom scores, or initial peak flow rates for the two groups. 2) Fifteen patients in the aminophylline group were hospitalized for an mean duration of 5.1+/-1.0 days, whereas 15 patients in the control group required 5.3+/-1.2 days. There were no significant differences between the two groups. 3) There was no differences in the absolute changes in their scores two scoring intervals(at 24 hours) between the two groups. 4) The two groups showed no differences in measurements of peak expiratory flow rates at any time interval and at the end of treatment. 5) The mean theophylline level for aminophylline group was 10.2+/-1.7micorgram/mL. 6) In the aminophylline group, 6 of 15 patients who entered the study experienced adverse effects consisting of nausea/vomiting, abdominal pain, and irritability. Five of 15 patients in the control group had an adverse effects. There were no significant differences between the two groups for incidence of adverse effects. 7) There were no significant differences between the two groups for amount of albuterol therapy required. CONCLUSION: When the combination of systemically administered corticosteroid and inhaled albuterol is used in hospitalized asthmatic children with mild to moderate asthma, addition of theophylline provided no additional benefit. Further study will be needed to evaluate if patients with more severe asthma exacerbation benefit for the use of intraveously administered aminophylline.
Abdominal Pain ; Administration, Oral ; Albuterol ; Aminophylline* ; Asthma* ; Child ; Continental Population Groups ; Hospitalization ; Humans ; Incidence ; Methylprednisolone ; Pediatrics ; Respiratory Rate ; Theophylline

AIMTo evaluate the hemodynamic effects of aminophylline and nifedipine in patients with HAPE.

METHODS10 patients with HAPE undergone Swan-Ganz catheter. The parameters of hemodynamics and arterial blood gases in HAPE were measured before and after administration of nifedipine 20 mg sublingually and aminophylline 0.25 g intravenously respectively.

RESULTSAfter administering 0.25 g aminophylline the mPAP and PVR significantly decreased, the cardiac output and the level of PaO2, SaO2 increased obviously, the mSAP, HR did not change so much. After using 20 mg nifedipine, the mPAP, PVR and mSAP also decreased, while the cardiac output, HR and the level of PaO2, SaO2 did not show any changes.

CONCLUSIONBoth of aminophylline and nifedipine can attenuate pulmonary hypertension in patients with HAPE, but the effect of aminophylline was better than the effect of nifedipine.

Adult ; Altitude ; Altitude Sickness ; drug therapy ; Aminophylline ; administration & dosage ; therapeutic use ; Humans ; Hypertension, Pulmonary ; drug therapy ; Male ; Nifedipine ; administration & dosage ; therapeutic use ; Treatment Outcome

Though exercise T1-201 myocardial perfusion-scintigraphy is an important test in the diagnosis and evaluation of coronary artery disease, this test is limited in cases with poor physical conditions and unstable angina and the physical characteristics of thallium are not ideal for nuclear imaging of the myocardium. Recently, technetium-99m-labelled agent(99mTc-MIBI) has been developed to improved the quality of imaging and for easy usage in myocardial perfusion scan. Therefore, we performed dipyridamole 99mTc-MIBI myocardial scintigraphy and coronary angiography on 25 subjects who were suspeced to have coronary artery disease and the results obtanined were as follows ; 1) The overall diagnostic sensitivity of dipyridamole 99mTc-MIBI perfusion scintigraphy was 73.4%, while specificity was 66.7%. 2) Per vessel sensitivity for coronary artery disease diagnosis by the test was 71.4% and a per vessel specificity for coronary artery disease was 95.7%. 3) In all 75 coronary arteries, LAD had a sensitivity of 66.7%(10/15) and a specificity of 100%(10/10); RCA had a sensitivity of 75%(6/8) and a specificity of 82.4%(14/17); LCX had a sensitivity of 60%(3/5) and a specificity of 100%(20/20). 4) After infusion of dipyridamole, the most frequent adverse effect was chest pain which was seen in 8 cases(32%). The headache was seen in 7 cases(28%). Most of the symptoms were mild in severity and subsided spontaneously but 3 subjects were severe enough to require intravenous administration of aminophylline. In conclusion, dipyridamole 99m2011-06-17Tc-MIBI myocardial perfusion scintigraphy is a useful and safe test for diagnosis of coronary artery disease.
Administration, Intravenous ; Aminophylline ; Angina, Unstable ; Chest Pain ; Coronary Angiography ; Coronary Artery Disease* ; Coronary Vessels* ; Diagnosis ; Dipyridamole* ; Headache ; Myocardial Perfusion Imaging* ; Myocardium ; Perfusion ; Perfusion Imaging ; Sensitivity and Specificity ; Thallium

PURPOSE: The purpose of this study was to evaluate the effects of theophylline in preterm infants with apnea on glucose homeostasis and insulin values. METHOD: In this prospective study, level of glucose and insulin were measured from peripheral blood of 8 neonates(1,450+/-114gm, 31+/-2.1week), who were admitted from April 1, 1997 to July 30, 1997 in Neonatal Intensive Care Unit of Wonkwang University Hospital, for apnea of prematurity(> 20 sec with bradycardia and/or cyanosis) were given aminophylline intravenously. Blood samples were collected at pretreatment, posttreatment 2hours, 1-2days, 3-4days, 5-7days and posttreatment 48hours, and compare to those of the 8 control neonates(1,711+/-232gm, 32+/-1.7week). RESULTS: The results were as follows: 1) Plasma glucose values were significantly higher in the treatment group than those of the control group at 1-2days(104.67+/-20.39mg/dL vs 83.43+/-15.86mg/dL) and 3-4days(111.0+/-32.39mg/dL vs 79.25+/-14.03mg/dL)(p<0.05). 2) Plasma glucose values which were increased at 1-2days(104.67+/-20.39mg/dL)and 3-4days(111.0+-32.39mg/dL), were significantly higher than pretreatment values(66.33+/-31.19mg/ dL)(p<0.02), but were not increased to the level of hyperglycemia(> 125mg/dL). 3) The mean posttreatment glucose levels drawn at 48hours after discontinuation of theophylline was significantly decreased to the values of pretreatment values compared to those of the 1-2days and 3-4days(p<0.01). 4) Insulin concentrations were also increased insignificantly when blood glucose were increased in the treatment group compared with control group. CONCLUSION: In conclusion, intravenous administration of theophylline produces hyperglycemia significantly, including an increase in a serum insulin. But, clinically significant hyperglycemia(> 125mg/dL) was not noted. So, plasma glucose may not need to be monitored in preterm apneic infants receiving theophylline. But, further studies are need to elucidate the effect of theophylline considering the serum toxic level of theophylline.
Administration, Intravenous ; Aminophylline ; Apnea* ; Blood Glucose* ; Bradycardia ; Glucose ; Homeostasis ; Humans ; Hyperglycemia ; Infant ; Infant, Newborn ; Infant, Premature* ; Insulin* ; Intensive Care, Neonatal ; Plasma* ; Prospective Studies ; Theophylline

Aminophylline can elicit thermogenesis in rats or increase metabolic rate during cold stress in lambs. We tested the hypothesis that aminophylline would reduce the change in core body temperature during laparoscopic abdominal surgery requiring pneumoperitoneum. Fifty patients were randomly divided into an aminophylline group (n=25) and a saline control group (n=25). Esophageal temperature, index finger temperature, and hemodynamic variables, such as mean blood pressure and heart rate, were measured every 15 min during sevoflurane anesthesia. In the aminophylline group, esophageal temperatures at T45 (36.1+/-0.38 vs. 35.7+/-0.29, P=0.024), T60 (36.0+/-0.39 vs. 35.6+/-0.28, P=0.053), T75 (35.9+/-0.34 vs. 35.5+/-0.28, P=0.025), T90 (35.8+/-0.35 vs. 35.3+/-0.33, P=0.011), and T105 (35.8+/-0.36 vs. 35.1+/-0.53, P=0.017) and index finger temperatures at T15 (35.8+/-0.46 vs. 34.9+/-0.33, P<0.001), T30 (35.7+/-0.36 vs. 35.0+/-0.58, P=0.029), T45 (35.8+/-0.34 vs. 35.2+/-0.42, P=0.020), T60 (35.7+/-0.33 vs. 34.9+/-0.47, P=0.010), T75 (35.6+/-0.36 vs. 34.8+/-0.67, P=0.028), T90 (35.4+/-0.55 vs. 34.4+/-0.89, P=0.042), and T105 (34.9+/-0.53 vs. 33.9+/-0.85, P=0.024) were significantly higher than in the saline control group. Aminophylline is effective in maintaining the core temperature through a thermogenic effect, despite reduced peripheral thermoregulatory vasoconstriction.
Abdomen/surgery ; Aminophylline/*administration & dosage ; Body Temperature/*drug effects ; Female ; Humans ; Hypothermia/*etiology/physiopathology/*prevention & control ; Laparoscopy/*adverse effects ; Male ; Middle Aged ; Pneumoperitoneum, Artificial/*adverse effects ; Single-Blind Method ; Treatment Outcome

Aminophylline can elicit thermogenesis in rats or increase metabolic rate during cold stress in lambs. We tested the hypothesis that aminophylline would reduce the change in core body temperature during laparoscopic abdominal surgery requiring pneumoperitoneum. Fifty patients were randomly divided into an aminophylline group (n=25) and a saline control group (n=25). Esophageal temperature, index finger temperature, and hemodynamic variables, such as mean blood pressure and heart rate, were measured every 15 min during sevoflurane anesthesia. In the aminophylline group, esophageal temperatures at T45 (36.1+/-0.38 vs. 35.7+/-0.29, P=0.024), T60 (36.0+/-0.39 vs. 35.6+/-0.28, P=0.053), T75 (35.9+/-0.34 vs. 35.5+/-0.28, P=0.025), T90 (35.8+/-0.35 vs. 35.3+/-0.33, P=0.011), and T105 (35.8+/-0.36 vs. 35.1+/-0.53, P=0.017) and index finger temperatures at T15 (35.8+/-0.46 vs. 34.9+/-0.33, P<0.001), T30 (35.7+/-0.36 vs. 35.0+/-0.58, P=0.029), T45 (35.8+/-0.34 vs. 35.2+/-0.42, P=0.020), T60 (35.7+/-0.33 vs. 34.9+/-0.47, P=0.010), T75 (35.6+/-0.36 vs. 34.8+/-0.67, P=0.028), T90 (35.4+/-0.55 vs. 34.4+/-0.89, P=0.042), and T105 (34.9+/-0.53 vs. 33.9+/-0.85, P=0.024) were significantly higher than in the saline control group. Aminophylline is effective in maintaining the core temperature through a thermogenic effect, despite reduced peripheral thermoregulatory vasoconstriction.
Abdomen/surgery ; Aminophylline/*administration & dosage ; Body Temperature/*drug effects ; Female ; Humans ; Hypothermia/*etiology/physiopathology/*prevention & control ; Laparoscopy/*adverse effects ; Male ; Middle Aged ; Pneumoperitoneum, Artificial/*adverse effects ; Single-Blind Method ; Treatment Outcome

OBJECTIVE: To investigate the protective effect of aminophylline on cerebral injury induced by cardiopulmonary bypass (CPB) in infants. METHODS: Forty patients who underwent ventricular septal defect within 3 years old were randomly divided into 2 groups(20 cases in each group).Aminophylline group:aminophylline (5 mg/kg) was injected slowly via the vein after anesthesia and maintained at a dose of 0.5 mg/(kg.h) until the end of CPB. CONTROL GROUP: aminophylline was replaced by Ringer's lactated solution. Samples were obtained at the beginning of CPB (T(1)),the end of CPB (T(2)),6 h (T(3)) and 24 h (T(4)) after the operation to measure S-100 beta protein, NSE, tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and interleukin-10 (IL-10) concentration by ELISA in the 2 groups. RESULTS: Compared with the time point immediately before CPB, the S-100beta protein,NSE, TNF-alpha, and IL-8 concentration in the 2 groups began to increase with the start of CPB, reached a climax at the end of CPB (T(2)),decreased gradually 6 h after the termination of CPB(T(3)) and could not restore to the level before CPB at T(4)(24 h after the termination of CPB).IL-10 in the 2 groups both increased after the CPB. At T(2) and T(3), S-100beta protein,NSE, TNF-alpha, and IL-8 concentrations were significantly lower than those in the aminophylline group (P<0.05 or P<0.01), while IL-10 was just the opposite. CONCLUSION There is cerebral damage induced by CPB. Aminophylline may play a protective role in cerebral injury by modulating the balance between the pro-inflammatory factor and anti-inflammatory factor to reduce the level of S-100beta protein and NSE during CPB and open cardiac surgeries.
Aminophylline ; administration & dosage ; therapeutic use ; Brain Diseases ; etiology ; prevention & control ; Cardiopulmonary Bypass ; adverse effects ; Cardiovascular Surgical Procedures ; Child, Preschool ; Female ; Heart Septal Defects ; drug therapy ; surgery ; Humans ; Infant ; Injections, Intravenous ; Male ; Nerve Growth Factors ; blood ; Neuroprotective Agents ; therapeutic use ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; blood