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caffeine citrate (Cafnea)

✓ Approved

Phebra · Small Molecule · Small Molecule

What is caffeine citrate?

caffeine citrate is a small molecule developed by Phebra. It is approved for therapeutic indications via injectable (others) or oral (po).

Drug Profile

Brand NamesCafnea
CompanyPhebra
Drug ClassSmall Molecule
RouteInjectable (Others), Oral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Phebra

Therapeutic Indications

caffeine citrate is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Respiratory, thoracic and mediastinal disordersApnoea✓ Approved

Related Research Articles

PubMedFrontiers in nutrition2026-07-25

Acute caffeine ingestion and exercise performance in women: a systematic review and meta-analysis of menstrual-cycle phase and hormonal contraceptive status.

Zhu Jian J, Zhang Yinghui Y, Li Ming M, Fan Xiaohan X et al.

Acute caffeine ingestion is widely used to enhance exercise performance, but most evidence comes from male or mixed-sex cohorts. Whether menstrual-cycle phase or hormonal contraceptive status modifies caffeine's ergogenic effect in women remains unclear. Six databases were searched for randomized controlled trials examining acute caffeine ingestion and objective exercise performance outcomes in women. Methodological quality and risk of bias were assessed using a modified PEDro scale and RoB 2. Three-level meta-analyses accounted for dependent effect sizes within studies. The primary moderator was reproductive-hormonal status, classified as early follicular, late follicular/peri-ovulatory, luteal/mid-luteal, or hormonal contraceptive/oral contraceptive use. Exploratory analyses examined dose, exercise type, phase verification, timing, and habitual caffeine intake. Twenty studies contributed 144 primary effect sizes. Acute caffeine ingestion improved exercise performance in women overall (Hedges' g = 0.37, 95% CI 0.24 to 0.50), with moderate heterogeneity and a prediction interval crossing the null. Positive estimates were observed across all reproductive-hormonal strata, but there was no clear evidence of between-stratum moderation. The overall effect was robust to outlier exclusion and alternative correlation assumptions. Exploratory analyses suggested that exercise-task phenotype and phase-verification method may partly explain variability in observed effects, whereas dose, timing, and habitual caffeine intake did not support phase-specific prescriptions. Risk-of-bias concerns, sparse subgroup data, and low-to-very-low GRADE certainty limited individualized inference. Acute caffeine ingestion produces a small average ergogenic effect in women, but exploratory findings suggest that its expression may vary by exercise task within different reproductive-hormonal contexts. Current evidence therefore supports a context-sensitive interpretation rather than rigid menstrual-phase- or contraceptive-specific prescriptions. However, given the low-to-very-low certainty of evidence, these findings should be interpreted cautiously and considered hypothesis-generating. Inconsistent phase verification remains a key methodological limitation that may obscure biologically meaningful patterns. Future female-specific trials should combine rigorous hormonal verification, detailed contraceptive profiling, prespecified exercise phenotypes, and mechanistic assessment to refine individualized caffeine guidance.. OSF https://osf.io/5y69g/, identifier 5y69g.

PMID 42500255
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PubMedActa medica portuguesa2026-07-25

From Obesity to Bigorexia: A Clinical Case Report.

Eiras Inês I, Sousa Maria Inês MI, Bandeira Santos Ana A, Oliveira Filipe F et al.

Body image is a multidimensional construct about one's appearance. Social and media factors contribute to dissatisfaction and are associated with mental health disorders. In adolescence, obesity emerges as a significant factor, with a four-fold increased risk of body dissatisfaction. Muscle dysmorphia is characterized by an obsessive pursuit of muscularity and distorted body image. A 16-year-old male with a history of obesity and depression, medically accompanied since age 10, developed obsessive behaviors around diet and exercise after weight loss and remission of depression. He adopted a "bulking and cutting" regimen and used creatine, protein, and caffeine supplements. He displayed rigid behavior, with poor insight. Given the pervasive functional impairment, he was referred to child and adolescent psychiatry. Muscle dysmorphia, classified as a body dysmorphic disorder, is underdiagnosed. Adolescent obesity may be a predisposing factor. Early recognition, particularly in adolescents with obesity and body image concerns is crucial for healthy development.

PMID 42497843
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PubMedFrontiers in endocrinology2026-07-25

Clinical, metabolomic, and proteomic profiles associated with reproductive outcomes in unexplained recurrent pregnancy loss.

Song Zicheng Z, Jiang Yishi Y, Zhu Zhixing Z, Che Yan Y et al.

To identify preconception clinical and multi-omics factors associated with conception and early pregnancy loss in women with unexplained recurrent pregnancy loss (URPL). In this prospective cohort study, 149 women with URPL selected from 420 outpatients based on guideline-recommended criteria were enrolled between November 2024 and May 2025 and followed-up for 12 months. Preconception fasting plasma was analyzed for clinical biomarkers, untargeted metabolomics, and data-independent acquisition proteomics. Outcomes included conception, ongoing pregnancy beyond 12 weeks and early pregnancy loss before 12 weeks. Multivariable logistic regression was used to evaluate the associations of clinical and multi-omics factors with reproductive outcomes, adjusting for maternal age, body mass index, number of prior losses, and use of assisted reproductive technology. Of 149 women, 99 conceived (66.4%) during the follow-up. By 12 weeks of gestation, 67 (67.7%) had ongoing pregnancies and 32 (32.3%) experienced early pregnancy loss. Higher testosterone was associated with lower probability of conception (adjusted odds ratio [aOR] 0.50, 95% confidence interval [CI] 0.28-0.89, p = 0.019). Women who conceived showed higher levels of progesterone-related metabolites, including 17-hydroxyprogesterone (fold change, FC = 3.89), pregnanediol 3-O-glucuronide (FC = 2.37), and pregnanetriol 3α-O-β-D-glucuronide (FC = 2.39). Among women who conceived, higher prolactin was associated with higher odds of early pregnancy loss (aOR 1.09, 95% CI 1.01-1.18, p = 0.036), and anti-phosphatidylserine/prothrombin showed a borderline association (aOR 1.07, 95% CI 1.00-1.14, p = 0.052). Early pregnancy loss was characterized by lower bile acid-related metabolites and higher caffeine and methylxanthine metabolites. Proteomic analysis showed enrichment of bile acid biosynthetic process. After adjustment, higher 7α,12α-dihydroxy-3-oxocholest-4-en-27-oic acid was associated with lower odds of early pregnancy loss (aOR 0.64, 95% CI 0.44-0.95, p = 0.025). Higher testosterone was associated with lower odds of conception. Among women who conceived, early pregnancy loss was associated with higher prolactin, borderline higher anti-PS/PT, lower bile acid-related metabolites, and higher caffeine-related metabolites, with 7α,12α-dihydroxy-3-oxocholest-4-en-27-oic acid identified as an exploratory metabolomic candidate. These findings suggest that potential androgen-related biology, prolactin, non-criteria antiphospholipid antibodies, and bile acid metabolism may be associated with reproductive outcomes in URPL, warranting validation in independent cohorts.

PMID 42500125
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PubMedNational science review2026-07-25

Metal-defect pairs for near-stoichiometric electrocatalytic C-N coupling.

Wu Yandong Y, Chen Wei W, Zou Yuqin Y, Wang Jinbo J et al.

Geminal-site catalysts (GSCs) are prospective candidates for fulfilling the goal of aqueous electrochemical reductive cross-coupling reactions (ERCR) at near-stoichiometric yields. Nevertheless, a problem lies in the lack of a synthetic route for GSCs with few single sites. Here we report a defect-accompanying strategy for synthesizing GSCs containing metal-defect catalytic pairs (M-D GSCs), meaning that Fe-D GSCs can realize the electrochemical synthesis of cyclohexanone oximes (CHOs) from high concentrations (0.5 M) of nitrites (NO2 -) and cyclohexanone (CYC) at near-stoichiometric yields (the Faradic efficiency or yieldC/N: 91.3%). Multiple in-/ex-situ characterizations demonstrated that metal-citrate complexes were converted to metal-defect catalytic pairs via the liberation of gaseous carbon/nitrogen species during pyrolysis. Furthermore, we developed an innovative cathodic oxime-alkali process, where high concentration NaNO2 and CYC can be electrochemically converted to high-purity products including NaOH and CHO. This work showcases the enormous potential of M-D GSCs in achieving near-stoichiometric conversion for ERCR reactions.

PMID 42500738
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PubMedPhoton science2026-07-25

Uncertainty-Aware Machine Learning for Small-Angle X‑ray Scattering Analysis in Autonomous Experimentation.

Cao Chuntian C, Kim Hyeong Jin HJ, Carbone Matthew R MR, Reyes Kristofer K et al.

Small-angle X-ray scattering (SAXS) is a powerful high-throughput characterization tool for probing nanoscale structure in native sample environments, providing real-time morphological information such as nanoparticle size and shape during synthesis. However, automated SAXS data analysis for extracting meaningful structural parameters is non-trivial and remains a bottleneck in closed-loop experimentation towards autonomous materials discovery, which demands fast, reliable, and uncertainty-aware data analysis. Here, we develop a machine-learning approach for automated SAXS analysis tailored to closed-loop nanoparticle synthesis. A Random Forest (RF) regression model is trained on 100,000 synthetic SAXS curves generated from polydisperse spherical nanoparticles with realistic background contributions. Using normalized one-dimensional SAXS intensity profiles as input, the RF model directly predicts nanoparticle radius, size polydispersity, and background parameters, while the ensemble standard deviation across trees provides built-in uncertainty quantification (UQ). On synthetic data, we show that combining fit-quality metrics (R2, MAE) with thresholds on prediction uncertainty reliably identifies accurate parameter estimates without access to ground truth. We then apply the trained model to 365 experimental SAXS profiles of citrate-reduced gold nanoparticles synthesized using an automated droplet-flow microreactor with in situ SAXS at a synchrotron beamline, classifying the results into high- and low-confidence subsets based on UQ metrics. Finally, we integrate RF-based SAXS analysis into a simulated closed-loop optimization campaign using Gaussian process Bayesian optimization to minimize nanoparticle polydispersity, benchmarking against conventional automated Levenberg-Marquardt fitting. The RF-guided campaign exhibits substantially faster convergence and lower relative opportunity cost (∼0.07 vs ∼0.3), demonstrating that uncertainty-aware machine-learning SAXS analysis significantly enhances the efficiency and robustness of autonomous nanomaterials synthesis workflows.

PMID 42499321
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PubMedNeuroSci2026-07-24

Effect of Caffeine on Cell Death, Oxidative Stress, and Microglial Morphology in a Ferret Organotypic Brain Slice Model of Hypoxia-Ischemia.

Brandon Olivia C OC, Corry Kylie A KA, Jin Zheyu Ruby ZR, DiNucci Kate F KF et al.

Brain injury after hypoxia-ischemia (HI) is the leading cause of morbidity and mortality in term and near-term neonates worldwide. The ferret is a promising translational model to study HI due to its gyrified brain and white-to-gray matter ratio that more closely resembles humans compared to rodents. Caffeine, an adenosine A2A receptor (A2AR) antagonist, shows neuroprotective potential after HI, but its effects have not been fully characterized. We sought to evaluate caffeine's effect on neuronal cell death, cytotoxicity, and inflammatory and oxidative stress markers in a term-equivalent ferret organotypic brain slice model of HI. Slices were cultured for 72 h, exposed to two hours of oxygen-glucose deprivation (OGD), and randomized to OGD alone, OGD with caffeine (20 or 50 mg/L), or OGD with caffeine and an A2AR agonist. Healthy slices served as controls. Outcomes included global cell death, regional cell death, microglial morphology, and expression of inflammatory and oxidative stress genes (46-48 slices/group for cell death assays and 18 slices/group for imaging, balanced by sex). Caffeine 50 mg/L significantly reduced global cell death compared to OGD (p = 0.02), and this effect persisted despite co-administration of an A2AR agonist (p = 0.01), suggesting that protection was not primarily mediated through A2AR signaling. Caffeine also did not change regional pyknotic nuclei counts (p > 0.05). Caffeine altered microglial morphology, increasing the proportion of microglia with features characteristic of control conditions. OGD significantly increased expression of inflammatory and oxidative stress-related genes (p < 0.05) compared with control slices, whereas caffeine did not significantly alter gene expression. In summary, caffeine partially reversed global cell death after OGD and altered microglial morphology. Larger, higher-powered studies are needed to further investigate caffeine's effects on neonatal HI.

PMID 42496326
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