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theophylline

✓ Approved

Bausch Health Companies Inc. · ADORA1 · 小分子

什么是 theophylline？

theophylline 是一种小分子，由Bausch Health Companies Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

公司Bausch Health Companies Inc.
药物类别小分子
分子靶点ADORA1, ADORA2A
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Bausch Health Companies Inc.

作用机制

分子靶点

theophylline 作用于 2 个分子靶点：

ADORA1adenosine A1 receptor (RDC7)
ADORA2Aadenosine A2a receptor (A2aR, RDC8)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

theophylline 针对 3 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Respiratory, thoracic and mediastinal disordersAsthma✓ Approved
Respiratory, thoracic and mediastinal disordersBronchitis chronic✓ Approved
Respiratory, thoracic and mediastinal disordersEmphysema✓ Approved

相关研究文献

PubMedThe journal of physical chemistry letters2026-10-23

Predicting Aqueous Solubility of Pharmaceutical Cocrystals Using Constant Chemical Potential Enhanced Sampling Simulations.

Neha, Bjelobrk Zoran Z, Karmakar Tarak T

We present an integrated molecular simulation framework that combines molecular dynamics, enhanced sampling, and constant chemical potential simulations to uncover growth and dissolution mechanisms of molecular cocrystals and predict equilibrium solubility, using the theophylline-aspirin (THE-ASP) cocrystal as a prototypical system. Solubility is determined by sampling the growth and dissolution of ASP and THE molecules at a dimeric kink site on the crystal surface and computing the free-energy differences between their dissolved and crystalline states as a function of solution composition. These free-energy differences are interpreted as effective chemical potentials of the respective molecular species, and the solubility is identified as the solution composition at which the sum of the effective chemical potentials of ASP and THE equals zero. To address the large conformational and orientational freedom inherent to these molecules, we introduce collective variables that incorporate atomic density, molecular orientation, and solvent coordination, which, when used in Well-tempered Metadynamics simulations, enable efficient sampling of growth and dissolution processes and the calculation of well-converged free-energy surfaces. The calculated free energy profiles reveal asymmetric thermodynamic driving forces, with aspirin favoring incorporation into the crystal and theophylline preferentially stabilizing in solution, providing molecular-level insight into cocrystal growth dynamics. The predicted equilibrium solubility of the THE-ASP cocrystal, χ* = 0.00063 ± 0.00014, lies between the reported aqueous solubilities of the individual components (ASP ≈ (3-5) × 10-4; THE ≈ (6-8) × 10-4 at 25 °C).

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PubMedForensic science international2026-10-23

Physicochemical and chemometric profiling of counterfeit Captagon tablets for seizure comparison and forensic intelligence.

Alabdalla Mahmoud A MA, As'ad Abdelqader S AS

Counterfeit Captagon tablets trafficked throughout the Near and Middle East rarely contain the original active ingredient, fenethylline. Instead, they commonly contain amphetamine and pharmacologically active adulterants. Whether tablet color and logo/shape reflect the underlying chemical profile remains unclear. A Primary Dataset of 50 tablets and an Independent Comparison Dataset of 31 tablets, derived from different submissions within a six-seizure collection from Jordan, were evaluated alongside case-level adulterant records covering 651 submitted tablets. Physical characteristics and semiquantitative gas chromatography-mass spectrometry profiles, expressed as normalized chromatographic peak-area percentages, were examined using correlation analysis, principal component analysis, hierarchical cluster analysis, one-way analysis of variance, Tukey post hoc comparisons, Kruskal-Wallis analysis, and a laboratory-prefix sensitivity analysis. The multivariate analyses showed substantial overlap among color and logo/shape groups. In the Primary Dataset, diphenhydramine normalized peak-area percentage differed among logo/shape categories (F(3, 43) = 8.80, p < 0.001, η² = 0.38), although 62% of the variance remained unexplained and the distributions overlapped. Tukey, Kruskal-Wallis (H = 17.95, p < 0.001), and laboratory-prefix sensitivity analyses supported the association. Caffeine, theophylline, and acetaminophen occurred in all six seizure cases, while several constituents differed between the tablet datasets. Tablet color did not provide a useful indication of chemical profile. Logo/shape showed a dataset-specific association with diphenhydramine, but group overlap and unavailable logo information for the comparison dataset precluded predictive or externally validated classification. Physical documentation may complement, but cannot replace, instrumental chemical profiling in forensic seizure comparison.

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PubMedToxicology and applied pharmacology2026-10-22

Estimation of respiration rate from nonclinical telemetry ECG data.

Sindhu Kavyakantha Remakanthakurup KR, Hotek Julia C JC, Ferraro Jude W JW, Port Russell G RG et al.

Assays to assess respiratory function are included in the ICH S7A guidance for Safety Pharmacology, which identifies the core in vivo studies required to evaluate safety prior to First in Human (FIH) dosing. This requirement is most commonly met using dedicated stand-alone rodent respiratory studies that require additional studies and increased resources. More importantly, the demonstrated transitional value of dedicated respiratory endpoints to predict risk and improve FIH safety is lacking. As such, alternative approaches that utilize commonly collected signals from cardiovascular assessment studies, such as electrocardiograms (ECG), to calculate respiration rate (RespRate) as a biomarker of potential adverse effects are becoming increasingly relevant. In this study, we implement three algorithms developed to estimate ECG-derived RespRate (EDR) in humans on preclinical ECG data collected from dogs. We then compare EDR to the benchmark direct measure of RespRate derived from telemetry intra-thoracic pressure (ITP) sensors in 19 recordings. EDR obtained using the moment-based and principal component-based algorithms was not significantly different from the benchmark, based on a TOST (two one-sided tests) analysis with an equivalence margin of five breaths/min, in 100% and 89% of animals respectively. Furthermore, in a positive control study administering Theophylline, the PCA method detected a drug-induced increase in RespRate also present in the ITP data. Thus, EDR may provide a potential alternative to stand-alone respiratory assays, but further evaluation across a broader range of respiration changes, subjects, and ECG hardware is needed to establish the robustness of these algorithms.

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PubMedJournal of separation science2026-10-22

A Validated Multi-Analyte Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Therapeutic Drug Monitoring and Targeted Toxicological Assessment of 54 Drugs and Metabolites in Human Serum.

Kratka Katerina K, Sistik Pavel P, Jerga Radek R, Olivkova Ivana I et al.

Therapeutic drug monitoring and targeted toxicological assessment require quantitative methods capable of covering chemically diverse drugs over clinically relevant concentration ranges. We developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of 54 analytes in human serum, including antiepileptic drugs, antidepressants, antipsychotics, benzodiazepines, antifungal agents, theophylline, and selected clinically relevant metabolites. Serum samples were prepared by protein precipitation with perchloric acid. Chromatographic separation was achieved on an ACQUITY UPLC BEH C18 column using water/methanol mobile phases containing 2 mM ammonium acetate. Detection was performed in polarity-switching selected reaction monitoring mode using two transitions per analyte and 28 isotope-labeled or structurally related internal standards. The total run time was 8.5 min. Analyte-specific calibration models and validated concentration ranges covered 0.1-22,500 ng/mL, depending on the analyte. The method demonstrated acceptable selectivity, calibration performance, accuracy, precision, matrix effects, and stability under routine handling and storage conditions for analytes with available data. Within-run and between-run precision did not exceed 14.3% and 13.9%, respectively. Matrix effects ranged from -8.35% to +10.25%. Application to 120 remnant patient serum samples supported the feasibility of multiplex measurement of drugs from several therapeutic classes in a single analytical run. The method is suitable for routine serum-based therapeutic drug monitoring and for targeted toxicological interpretation of a predefined analyte panel.

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PubMedACS omega2026-10-17

ChemODE: A Physics-Informed Neural Surrogate for Robust Pharmacokinetics and Biochemical Dynamics.

Kulvutiroj Wit W

The automated discovery of governing kinetic laws from observational data is a critical challenge in systems biology, pharmacology, and chemical engineering. In these experimental domains, data-driven mechanism discovery is complicated by sparse sampling, measurement noise (e.g., blood assays), and the prevalence of nonlinear saturation limits (Michaelis-Menten kinetics). Existing symbolic regression methods, such as SINDy, rely on polynomial basis functions that fundamentally fail to extrapolate physical saturation, and their reliance on numerical differentiation degrades catastrophically in high-noise regimes (>5%). In this work, we introduce ChemODE, a physics-informed gray-box framework tailored for biochemical and pharmacokinetic (PK) networks. ChemODE integrates (1) Constrained Rational Layers to autonomously enforce physical saturation laws, (2) On-the-fly Feature Normalization to resolve magnitude bias in multicompartment scale separations, and (3) a noise-robust integral-based optimization scheme. We validate ChemODE on fundamental biological benchmarks, including the nonlinear Brusselator limit cycle and a synthetic 3-compartment pharmacokinetic model. To demonstrate clinical applicability, ChemODE successfully extracts physiological absorption and elimination rates from real-world human theophylline pharmacokinetic assays. Furthermore, rigorous uncertainty quantification (10-seed ensembles) proves that ChemODE recovers enzyme kinetics with high precision (V max error ≈ 1%), significantly outperforming unconstrained baselines. This work establishes that integral-based minimization, combined with rational architectural constraints and a neural residual paradigm, provides a robust surrogate modeling path for interpretable mechanism discovery in noise-dominated biochemical settings.

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PubMedInternational immunopharmacology2026-10-16

Ensifentrine inhibits lipopolysaccharide-induced production of cytokines by human lung macrophages: a comparison with roflumilast, and an interaction with adenosine.

Brollo M M, Salvator H H, Glorion M M, Marquant Q Q et al.

The dual phosphodiesterase (PDE) 3/4 inhibitor ensifentrine was recently approved for the maintenance treatment of chronic obstructive pulmonary disease in adults. Ensifentrine anti-inflammatory effects have not been studied in human lung macrophages (LMs), which are critically involved in respiratory disease. The main objectives of the present study were to compare the inhibitory effects of ensifentrine, the PDE4 inhibitor roflumilast, and the non-selective PDE inhibitor theophylline on the lipopolysaccharide (LPS)-induced production of cytokines by LMs and to assess interactions with the adenosine analogue 5´-N-ethyl-carboxamidoadenosine (NECA). LMs isolated from resected human lungs were incubated with a range of concentrations of ensifentrine, roflumilast, theophylline, NECA, and formoterol, and stimulated with LPS for 24 h. The levels of tumour necrosis factor-alpha (TNF-α), CCL2, CCL3, and CCL4 in the culture supernatants were measured using ELISAs. Ensifentrine reduced the LPS-stimulated production of TNF-α by LMs in a concentration-dependent manner, with a 100-fold lower potency but a 20-30% higher efficacy than roflumilast. Theophylline and formoterol were essentially inactive. The relative reductions in the LPS-induced production of TNF-α and the three CCL chemokines associated with treatment with the two selective inhibitors was further accentuated by NECA and resulted in similar levels of cytokine production inhibition (between 65% and 95%) with the two PDE inhibitors. Clinically relevant concentrations of ensifentrine and roflumilast partially inhibited the LPS-induced production of cytokines by LMs - cytokine production that might be enhanced during inflammatory flare-ups of respiratory diseases.

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