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  1. In vivo/in vitro correlation of experimental sustained-release theophylline formulations
    Yuen KH, Desmukh AA, Newton JM
    Pharm Res, 1993 Apr;10(4):588-92.
    PMID: 8483843
    A novel multiparticulate sustained-release theophylline formulation, which consisted of spherical drug pellets coated with a rate-controlling membrane, was evaluated in vivo. Two preparations that differ solely in the coat thickness, and hence rate of in vitro drug release, were studied in comparison with a solution of the drug. Both preparations produced serum concentration profiles that are reflective of a slow and sustained rate of absorption. The in vivo release versus time profiles calculated using a deconvolution procedure showed that the two preparations differed in the rate but not the extent of drug release. Satisfactory correlation was also obtained between the in vivo and the in vitro results. When the two preparations were further compared using the parameters, time to reach peak concentration (Tp), peak concentration (Cp), and total area under the serum concentration versus time curves (AUC), a statistically significant difference was observed in the Tp and Cp values but not the AUC values, suggesting that the preparations differed in the rate but not the extent of absorption. In addition, the extent of absorption from both preparations was comparable to that obtained with the drug solution.
    Matched MeSH terms: Theophylline/blood; Theophylline/pharmacokinetics*
  2. The diuretic effect of adding aminophylline or theophylline to furosemide in pediatric populations: a systematic review
    Van Siang Lian Mang P, Hui JC, Tan RSJ, Hasan MS, Choo YM, Abosamak MF, et al.
    Eur J Pediatr, 2023 Jan;182(1):1-8.
    PMID: 36251063 DOI: 10.1007/s00431-022-04655-w
    The diuretic effect of the combined furosemide and aminophylline/theophylline among pediatric patients remains unclear. The primary aim of this systematic review was to examine the clinical diuretic effects (urine output and fluid balance) of co-administration of furosemide and aminophylline/theophylline as compared to furosemide alone in pediatric population. Ovid MEDLINE, CENTRAL, and EMBASE were searched from its inception until March 2022 for observational studies and randomized controlled trials (RCTs) comparing the administration of furosemide versus furosemide and aminophylline/theophylline in pediatric population. Case reports, case series, commentaries, letters to editors, systematic reviews, and meta-analyses were excluded. Five articles with a total sample population of 187 patients were included in this systematic review. As compared to the furosemide alone, our pooled data demonstrated that co-administration of furosemide and aminophylline/theophylline was associated with higher urine output (mean difference: 2.91 [90% CI 1.54 to 4.27], p 
    Matched MeSH terms: Theophylline*
  3. Topological characterization of a bacterial cellulose-acrylic acid polymeric matrix
    Halib N, Mohd Amin MC, Ahmad I, Abrami M, Fiorentino S, Farra R, et al.
    Eur J Pharm Sci, 2014 Oct 1;62:326-33.
    PMID: 24932712 DOI: 10.1016/j.ejps.2014.06.004
    This paper focuses on the micro- and nano-topological organization of a hydrogel, constituted by a mixture of bacterial cellulose and acrylic acid, and intended for biomedical applications. The presence of acrylic acid promotes the formation of two interpenetrated continuous phases: the primary "pores phase" (PP) containing only water and the secondary "polymeric network phase" (PNP) constituted by the polymeric network swollen by the water. Low field Nuclear Magnetic Resonance (LF NMR), rheology, Scanning Electron Microscopy (SEM) and release tests were used to determine the characteristics of the two phases. In particular, we found that this system is a strong hydrogel constituted by 81% (v/v) of PP phase the remaining part being occupied by the PNP phase. Pores diameters span in the range 10-100 μm, the majority of them (85%) falling in the range 30-90 μm. The high PP phase tortuosity indicates that big pores are not directly connected to each other, but their connection is realized by a series of interconnected small pores that rend the drug path tortuous. The PNP is characterized by a polymer volume fraction around 0.73 while mesh size is around 3 nm. The theoretical interpretation of the experimental data coming from the techniques panel adopted, yielded to the micro- and nano-organization of our hydrogel.
    Matched MeSH terms: Theophylline/chemistry
  4. Investigating how amine structure influences drug-amine ion-pair formation and uptake via the polyamine transporter in A549 lung cells
    Mohamed Sofian Z, Harun N, Mahat MM, Nor Hashim NA, Jones SA
    Eur J Pharm Biopharm, 2021 Nov;168:53-61.
    PMID: 34455038 DOI: 10.1016/j.ejpb.2021.08.003
    Transiently associating amines with therapeutic agents through the formation of ion-pairs has been established both in vitro and in vivo as an effective means to systemically direct drug delivery to the lung via the polyamine transport system (PTS). However, there remains a need to better understand the structural traits required for effective PTS uptake of drug ion-pairs. This study aimed to use a structurally related series of amine counterions to investigate how they influenced the stability of theophylline ion-pairs and their active uptake in A549 cells. Using ethylamine (mono-amine), ethylenediamine (di-amine), spermidine (tri-amine) and spermine (tetra-amine) as counterions the ion-pair affinity was shown to increase as the number of protonated amine groups in the counterion structure increased. The mono and diamines generated a single hydrogen bond and the weakest ion-pair affinities (pKFTIR: 1.32 ± 0.04 and 1.43 ± 0.02) whereas the polyamines produced two hydrogen bonds and thus the strongest ion-pair affinities (pKFTIR: 1.93 ± 0.05 and 1.96 ± 0.04). In A549 cells depleted of endogenous polyamines using α-difluoromethylornithine (DFMO), the spermine-theophylline uptake was significantly increased (p 
    Matched MeSH terms: Theophylline/metabolism*
  5. Fulltext Theophylline toxicity: A case report of the survival of an undiagnosed patient who presented to the emergency department
    Mohamad N, Abd Halim NN, Ahmad R, Baharuddin KA
    Malays J Med Sci, 2009 Apr;16(2):33-7.
    PMID: 22589656 MyJurnal
    Theophylline toxicity is a life-threatening toxidrome that can present to an emergency department. To ascertain an immediate provisional diagnosis in toxicology at the emergency department is very challenging, especially when the patient presents with altered mental status, because the clinical features of several toxidromes overlap. We report a case of survival of undiagnosed theophylline toxicity that required intubation for two days in the intensive care unit. This was the first case to have been reported from our department. Accurate diagnosis of a toxidrome by gaining adequate history and conducting a thorough physical examination and early serum toxicology screening, coupled with good knowledge of toxicology, will lead to better patient outcomes.
    Matched MeSH terms: Theophylline
  6. Asthma control in the Asia-Pacific region: the Asthma Insights and Reality in Asia-Pacific Study
    Lai CK, De Guia TS, Kim YY, Kuo SH, Mukhopadhyay A, Soriano JB, et al.
    J Allergy Clin Immunol, 2003 Feb;111(2):263-8.
    PMID: 12589343
    Few data on asthma management are available for the Asia-Pacific region.
    Matched MeSH terms: Theophylline/therapeutic use
  7. Use of artificial neural networks to predict drug dissolution profiles and evaluation of network performance using similarity factor
    Peh KK, Lim CP, Quek SS, Khoh KH
    Pharm Res, 2000 Nov;17(11):1384-8.
    PMID: 11205731
    PURPOSE: To use artificial neural networks for predicting dissolution profiles of matrix-controlled release theophylline pellet preparation, and to evaluate the network performance by comparing the predicted dissolution profiles with those obtained from physical experiments using similarity factor.

    METHODS: The Multi-Layered Perceptron (MLP) neural network was used to predict the dissolution profiles of theophylline pellets containing different ratios of microcrystalline cellulose (MCC) and glyceryl monostearate (GMS). The concepts of leave-one-out as well as a time-point by time-point estimation basis were used to predict the rate of drug release for each matrix ratio. All the data were used for training, except for one set which was selected to compare with the predicted output. The closeness between the predicted and the reference dissolution profiles was investigated using similarity factor (f2).

    RESULTS: The f2 values were all above 60, indicating that the predicted dissolution profiles were closely similar to the dissolution profiles obtained from physical experiments.

    CONCLUSION: The MLP network could be used as a model for predicting the dissolution profiles of matrix-controlled release theophylline pellet preparation in product development.

    Matched MeSH terms: Theophylline/chemistry*
  8. Fulltext Comparing Efficacy and Safety of Empirical vs. Guided Therapy for Non-cardiac Chest Pain: A Pragmatic Randomized Trial
    Abdul Kadir NP, Ma ZF, Abdul Hafidz MI, Annamalai C, Jayaraman T, Hamid N, et al.
    Front Med (Lausanne), 2021;8:605647.
    PMID: 33659261 DOI: 10.3389/fmed.2021.605647
    Background: Non-cardiac chest pain is common with two-thirds due to gastroesophageal reflux disease (GERD). Objective: To evaluate the effectiveness and safety of guided vs. empirical therapy in non-cardiac chest pain. Methods: Adults with normal angiogram or stress test were randomized into either a guided or empirical group. In the guided group, after the ambulatory pH-impedance test, if GERD then dexlansoprazole 30 mg/day for 8 weeks, but if functional or hypersensitive chest pain, then theophylline SR 250 mg/day for 4 weeks. In the empirical group, dexlansoprazole 60 mg/day was given for 2 weeks. The primary outcome was global chest pain visual analog score (VAS) and secondary outcomes were Quality of Life in Reflux and Dyspepsia (QOLRAD), GERD questionnaire (GERDQ), and pH parameters, all determined at baseline, 2nd and 8th weeks. Results: Of 200 screened patients, 132 were excluded, and of 68 randomized per-protocol, 33 were in the guided group and 35 in the empirical group. For between-group analysis, mean global pain scores were better with guided vs. empirical group at 8th week (P = 0.005) but not GERDQ or QOLRAD or any of pH measures (all P > 0.05). For within-group analysis, mean QOLRAD improved earliest at 8th week vs. baseline (P = 0.006) in the guided group and 2nd week vs. baseline (P = 0.011) in the empirical group but no differences were seen in other secondary outcomes (P > 0.05). No serious adverse events were reported. Conclusions: Guided approach may be preferred over short-term empirical therapy in symptom response, however QOLRAD, acid-related symptoms, or pH measures are not significantly different (trial registration ID no. NCT03319121).
    Matched MeSH terms: Theophylline
  9. A stepwise approach to the management of chronic obstructive pulmonary disease
    Liam CK
    Family Physician, 1993;5:46-53.
    Smoking cessation helps patients with COPD more than any specific medical treatment. By commencing treatment early, the main symptoms of COPD, i.e. cough, dyspnoea, and excessive mucus production, can be relieved and premature mortality from respiratory failure can, in many cases, be prevented. An anticholinergic aerosol offers the greatest bronchodilator benefit with the least side-effects to a patient with COPD. After maximising the dosage of an anticholinergic agent, either an inhaled beta2-agonist or oral theophylline may be added for additional bronchodilator effects. Corticosteroids may be beneficial in a subset of the patients. Selected patients with exercise limitation despite optimal medical therapy may gain from an increased sense of well-being enrolled in a supervised exercise rehabilitation progromrne. Long-term domiciliary oxygen therapy improves survival for patients who are chronically hypoxaemic. Antibiotics are reserved for acute exacerbations. The role of alpha-1-antitrypsin replacement and lung transplantation is still investigational.
    Matched MeSH terms: Theophylline
  10. Highly electrochemically active Ti3C2Tx MXene/MWCNT nanocomposite for the simultaneous sensing of paracetamol, theophylline, and caffeine in human blood samples
    Mari E, Duraisamy M, Eswaran M, Sellappan S, Won K, Chandra P, et al.
    Mikrochim Acta, 2024 Mar 20;191(4):212.
    PMID: 38509344 DOI: 10.1007/s00604-024-06273-9
    The facile fabrication is reported of highly electrochemically active Ti3C2Tx MXene/MWCNT (3D/1D)-modified screen-printed carbon electrode (SPE) for the efficient simultaneous electrochemical detection of paracetamol, theophylline, and caffeine in human blood samples. 3D/1D Ti3C2Tx MXene/MWCNT nanocomposite was synthesized using microwave irradiation and ultrasonication processes. Then, the Ti3C2Tx/MWCNT-modified SPE electrode was fabricated and thoroughly characterized towards its physicochemical and electrochemical properties using XPS, TEM, FESEM, XRD, electrochemical impedance spectroscopy, cyclic voltammetry, and differential pulse voltammetry techniques. As-constructed Ti3C2Tx-MWCNT/SPE offers excellent electrochemical sensing performance with good detection limits (0.23, 0.57, and 0.43 µM) and wide linear ranges (1.0 ~ 90.1, 2.0 ~ 62.0, and 2.0-90.9 µM) for paracetamol, caffeine, and theophylline, respectively,  in the human samples. Notably, the non-enzymatic electroactive nanocomposite-modified electrode has depicted a semicircle Nyquist plot with low charge transfer resistance (Rct∼95 Ω), leading to high ionic diffusion and facilitating an excellent electron transfer path. All the above results in efficient stability, reproducibility, repeatability, and sensitivity compared with other reported works, and thus, it claims its practical utilization in realistic clinical applications.
    Matched MeSH terms: Theophylline
  11. Rheological behavior of biodegradable N-succinyl chitosan-g-poly (acrylic acid) hydrogels and their applications as drug carrier and in vitro theophylline release
    Bashir S, Teo YY, Ramesh S, Ramesh K, Mushtaq MW
    Int J Biol Macromol, 2018 Oct 01;117:454-466.
    PMID: 29807081 DOI: 10.1016/j.ijbiomac.2018.05.182
    Novel pH sensitive N-succinyl chitosan-g-poly (acrylic acid) hydrogels were synthesized through free radical mechanism. Rheometer was used to observe the mechanical strength of the hydrogels. In vitro degradation was conducted in SIF (pH 7.4). The effect of concentration of monomers, initiator, and crosslinking agent and pH and ionic strength of NaCl, CaCl2, and AlCl3 on swelling of the hydrogels was observed. The results showed that equilibrium swelling ratio was highly influenced by concentration of monomers, initiator, and crosslinking agent concentration, and pH and salt solutions of NaCl, CaCl2, and AlCl3. The swelling kinetics revealed that swelling followed non-Fickian anomalous transport. Furthermore, theophylline loading (DL %) and encapsulation efficiency (EE %) of the hydrogels was in the range of 15.5 ± 0.15-22.8 ± 0.06% and 62 ± 0.15-91 ± 0.26%, respectively. The release of theophylline in physiological mediums was strongly influenced by the pH. The theophylline release was in the range of 51 ± 0.20-92 ± 0.12% in SIF and 7.4 ± 0.02-14.9 ± 0.03% in SGF (pH 1.2), respectively. The release data fitted well to Korsmeyer-Peppas model. The chemical activity of the theophylline suggested that drug maintained its chemical activity after release in vitro. The results suggest that synthesized hydrogels are excellent drug carriers.
    Matched MeSH terms: Theophylline/pharmacology*
  12. Fulltext Morbidity associated with asthma and audit of asthma treatment in out-patient clinics
    Lim TO, Suppiah A, Ismail F, Selvan T, Khan NKI, Ngah BA
    Singapore Med J, 1992 Apr;33(2):174-6.
    PMID: 1621123
    A study was undertaken to determine the extent of morbidity associated with asthma and to audit the management of asthma in two out-patient clinics of two district hospitals. Patients were recruited for the study during a 3-month period from December 1990 to February 1991. Seventy asthmatic patients were studied. Eighty-six percent of the patients had their sleep disturbed by asthma, 77% took daily medication regularly, 63% felt that their activities were restricted by asthma, 60% had at least one acute exacerbation in the preceding six months. Of those who had their peak expiratory flow rate (PEFR) measured, 40% had a PEFR below 50% predicted, and only 11% had normal PEFR (greater than 80% predicted). The morbidity of asthma was thus considerable. On the other hand, the drug treatment of these asthmatics was grossly inadequate. They were prescribed on average 2.1 item of drugs, which for most patients comprised an oral beta agonist and a theophylline. Only 43% of the patients received inhaler therapy, but no patients were given steroids, inhaled or oral. The drug treatment was unrelated to the severity of patients' asthma. Further, objective measurement of severity was under-used in the assessment of asthma, only 8.5% of patients ever had their PEFR recorded. This study has found that asthma is poorly managed in out-patient clinics. We need to improve the training of doctors in the optimal management of asthma.
    Study site: General outpatient clinics, district hospitals, Pahang, Malaysia
    Matched MeSH terms: Theophylline/therapeutic use
  13. Fulltext Clinical outcomes of theophylline use as add-on therapy in patients with chronic obstructive pulmonary disease: A propensity score matching analysis
    Wilairat P, Kengkla K, Thayawiwat C, Phlaisaithong P, Somboonmee S, Saokaew S
    Chron Respir Dis, 2018 12 19;16:1479973118815694.
    PMID: 30558448 DOI: 10.1177/1479973118815694
    To examine clinical outcomes of theophylline use in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA). Electronic data from five hospitals located in Northern Thailand between January 2011 and December 2015 were retrospectively collected. Propensity score (PS) matching (2:1 ratio) technique was used to minimize confounding factors. The primary outcome was overall exacerbations. Secondary outcomes were exacerbation not leading to hospital admission, hospitalization for exacerbation, hospitalization for pneumonia, and all-cause hospitalizations. Cox's proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI). After PS matching, of 711 patients with COPD (mean age: 70.1 years; 74.4% male; 60.8% severe airflow obstruction), 474 theophylline users and 237 non-theophylline users were included. Mean follow-up time was 2.26 years. Theophylline significantly increased the risk of overall exacerbation (aHR: 1.48, 95% CI: 1.11-1.96; p = 0.008) and exacerbation not leading to hospital admission (aHR: 1.47, 95% CI: 1.06-2.03; p = 0.020). Theophylline use did not significantly increase the risk of hospitalization for exacerbation (aHR: 1.11, 95% CI: 0.79-1.58; p = 0.548), hospitalization for pneumonia (aHR: 1.28, 95% CI: 0.89-1.84; p = 0.185), and all-cause hospitalizations (aHR: 1.03, 95% CI: 0.80-1.33; p = 0.795). Theophylline use as add-on therapy to ICS and LABA might be associated with an increased risk for overall exacerbation in patients with COPD. A large-scale prospective study of theophylline use investigating both safety and efficacy is warranted.
    Matched MeSH terms: Theophylline/administration & dosage*
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