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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

PubMedMedicine2026-11-11

Effects of caffeine supplementation on exercise-induced muscle damage: A systematic review.

Mercan Süleyman S, Şahin Kafkas Armağan A, Coşkun Ilgın Ali IA, Kafkas Muhammed Emin ME

Exercise-induced muscle damage (EIMD) commonly occurs following unaccustomed or high-intensity exercise and is characterized by delayed-onset muscle soreness, elevated muscle damage biomarkers, and transient declines in muscle function. Caffeine, a widely consumed ergogenic aid, has been proposed to mitigate these adverse effects; however, the evidence across studies remains equivocal. This systematic review aimed to synthesize findings from randomized controlled trials (RCTs) that investigated the effects of caffeine supplementation on markers of EIMD. Following preferred reporting items for systematic reviews and meta-analyses guidelines, a comprehensive search was conducted in PubMed, Scopus, and Google Scholar databases, supplemented by citation tracking. RCTs published between 2005 and 2025 that included human participants and reported direct or indirect indicators of EIMD were eligible. Fifteen RCTs (n = 222) were included and assessed for methodological quality using the PEDro scale. Caffeine doses ranged from 3 to 6 mg/kg. Among the 6 studies assessing delayed-onset muscle soreness, 4 reported significant reductions in perceived soreness within 24 to 48 hours post-exercise, whereas 2 found no effect or adverse responses. Eleven studies examined biochemical markers; most detected no significant differences between caffeine and placebo, while 2 observed higher creatine kinase levels in the caffeine group. Five studies evaluated functional performance; some indicated attenuation of decrements in maximal voluntary isometric contraction or isokinetic torque, although results were inconsistent. Caffeine supplementation may transiently reduce subjective muscle soreness and, under certain conditions, help preserve muscle function following EIMD, but its effects on biochemical markers are inconsistent. The overall efficacy appears to depend on factors such as exercise modality, dosage, timing, and inter-individual variability. Larger, well-controlled RCTs with standardized protocols are needed to clarify caffeine's role in muscle damage and recovery.

PMID 43012808
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PubMedZhonghua nan ke xue = National journal of andrology2026-11-11

[Effect of zinc selenium L-carnitine compound nutrient combined with tamoxifen citrate on routine semen parameters and sperm DNA fragmentation index in male infertility patients].

Xie Yuanzhi Y, Xin Meijiao M, Shi Nanxiang N, Shi Yimin Y et al.

Objective To explore the effect of zinc selenium L-carnitine compound nutrient combined with tamoxifen citrate on routine semen parameters and sperm DNA fragmentation index of male infertility patients with abnormal sperm DNA fragmentation index. Methods A total of 903 male infertile patients with sperm DFI (>15%) were selected and randomly divided into control group (453 cases) and combination group (450 cases). The control group was treated with vitamin E soft capsule, and the combination group was treated with zinc selenium L-carnitine compound nutrient combined with tamoxifen citrate. The percentages of normal morphology sperm, sperm volume, sperm concentration, percentage of forward moving sperm（PR）, percentage of non-forward moving sperm（NP）, and DFI of patients in the two groups were collected before treatment and 1, 2 and 3 months after treatment. The effective rates of combined medication treatment for patients with abnormal DFI in different age groups were compared. Results After 1 month of treatment in the combination group, PR increased significantly and DFI decreased significantly (P<0.01). After 2 months of treatment, compared with before treatment, PR (P<0.01) and NP increased (P<0.05), DFI decreased (P<0.01). After 3 months of treatment, the semen volume increased compared with before treatment (P<0.05), and DFI decreased continuously (P<0.01). However, there was no significant difference in the percentage of normal morphological sperm and sperm concentration compared with before treatment (P>0.05). In the control group, PR increased significantly after 1 and 2 months of treatment compared with before treatment (P<0.01, P<0.05), and DFI decreased significantly (P<0.001, P<0.01). However, there was no statistically significant difference in the percentage of normal morphological sperm, semen volume, sperm concentration, and NP compared with before treatment. There was no significant difference in any parameters after 3 months of treatment compared with before treatment (P>0.05). Before treatment, the differences in various parameters between the two groups were not significant (P>0.05). After 1 and 2 months of treatment, compared with the control group, the DFI of the combination group showed a significant decrease (P<0.01, P<0.05), and the differences in other parameters were not significant (P>0.05). After 3 months of treatment, the differences in various parameters between the two groups were not significant (P>0.05). Among the patients in the combination group with DFI>25%, the treatment effectiveness rate of patients aged ≥35 years was higher than that of those aged <35 years old (P<0.01); while among the patients in the combination group with 15%0.05). Conclusion The zinc selenium L-carnitine compound nutrient combined with tamoxifen citrate can improve PR and sperm DNA integrity of male infertility patients. Meanwhile, patients with higher baseline DFI values combined with older age have better therapeutic effects.

PMID 43012228
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PubMedAnalytical chemistry2026-11-11

GRIFFINs and GoBleNs: A Non-Fictional Tool for Identifying Trace Controlled Substance Surrogates in Complex Mixtures.

Holman Aidan P AP, Borak Larissa L, Kurouski Dmitry D

Drug overdose deaths have tripled over the past two decades, and methamphetamine remains the second most frequently identified drug involved in such fatalities. Within the United States, the Drug Enforcement Administration seizes tens of thousands of kg of clandestine powders, tablets, crystals, and liquids that may contain anywhere from 1-100% pure methamphetamine every year. Unfortunately, current portable techniques, such as Raman and infrared spectroscopy, fail to reliably identify methamphetamine and other analogs below ∼23 wt % due to interference from cutting agents. We introduce GRIFFINs, a tool for the gold-enhanced Raman identification for forensic field inspection of narcotics. GRIFFINs uses gold-blended nanoparticles (GoBleNs), a novel cationic, lipophilic-specific, and highly selective surface-enhanced Raman spectroscopic (SERS) substrate for the identification of low amounts (<23 wt %) of chemicals like alkylamines in complex matrices that mimic the components of real clandestine samples. Using machine learning, we trained the model on 10 independent dilution series for each of three controlled substance surrogates (phenylethylamine, serotonin, and dopamine) and three other SERS-responsive cutting agents (lidocaine, benzocaine, and caffeine) before testing at least 85 independent mixtures that mimic real evidence samples. The novel SERS substrate, GoBleNs, was mixed with HPLC-compatible samples before being analyzed with a commercially available, portable Raman spectrometer equipped with 830 nm excitation in less than 1 min. Using extreme gradient boosting discriminant analysis, limits of identification ranged between <0.1 and 0.1 wt % depending on the analyte. This study demonstrates the first application of SERS for improving the portable Raman analysis of trace amphetamine and tryptamine surrogates for seized drug analysis.

PMID 43010424
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PubMedBMC veterinary research2026-11-11

Effects of different feeding regimes on growth performance, antioxidant activity, rumen fermentation, rumen microbiota and rumen metabolism in beef cattle.

Lu Qi Q, Zhou Di D, Yang Rong R, Ban Yiming Y et al.

The feeding regime significantly impacts on the production performance, ruminal fluid microbiota, and metabolites of ruminants. However, studies comparing the microbial metagenomics and metabolites in ruminal fluid of beef cattle fed pasture-based grazing and housed total mixed ration (TMR) feeding regimes have rarely been reported. Forty healthy Guanling beef cattle were divided into two equal groups according to a randomized complete block design. The pasture-based grazing group (BG) was allowed to the grazing period was 08:00-18:00 at a natural ranch. The housed TMR feeding group (BB) was reared under a housed feeding system and fed a TMR diet. Each treatment consisted of 20 beef cattle, and the experimental period lasted for 90 d. The metagenomics and metabolomics were used analysis ruminal fluid microbiota and metabolism. The results indicated that the BB group showed significantly higher levels of average daily gain, total antioxidant capacity, catalase, 2,2-diphenyl-1-picrylhydrazyl scavenging activity, ammonia nitrogen, and volatile fatty acid (P < 0.05), whereas it had significantly lower levels of malondialdehyde and hydroxyl free radical relative to the BG group (P < 0.05). Compared with the BB group, the BG group exhibited a significantly increased (P < 0.05) abundance of Bacillota at the phylum level but a significantly decreased (P < 0.05) abundance of Prevotella at the genus level. The modules associated with these relative abundance levels (Reductive citrate cycle (Arnon-Buchanan cycle), and Guanine ribonucleotide degradation, GMP = > Urate) were significantly more important in the BG group (P < 0.05) than in the BB group. Glycosyltransferase 2_Glycos_transf_2 was significantly enriched in the BB group, whereas glycoside hydrolase (GH)3, GH78, and GH36 were significantly enriched in the BG group. Metabolomic analysis revealed that linoleic acid metabolism was the dominant pathway in the rumen. Overall, the housed TMR-fed cattle enhanced growth performance, antioxidant activity, rumen fermentation, and Prevotella abundance, whereas the pasture-based grazing fed cattle enhanced Bacillota abundance and linoleic acid metabolism.

PMID 43009984
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PubMedMedicine2026-11-11

Development and interpretable validation of a machine-learning model for edentulism risk in US adults: A cross-sectional study integrating five algorithms and dietary data from NHANES 2009-2014.

Wu Shiyuan S, Huang Muze M, Shen Zi-Han ZH, Fu Yaw-Syan YS et al.

Edentulism is an end-stage oral condition that severely impairs the quality of life and overall health of older adults. Using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), this study integrated multidimensional information - including sociodemographic factors, chronic disease history, and dietary characteristics - to develop and validate an interpretable machine learning model for accurate prediction of edentulism risk. A retrospective cross-sectional design was adopted, including 9230 NHANES participants aged ≥ 20 years from 2005 to 2018, among whom the prevalence of edentulism was 7.86%. Participants were split into training and testing sets using a 70%:30% stratified random allocation. LASSO regression was first applied to select 11 core variables from 44 candidate features: age, years of education, smoking status, poverty-to-income ratio (PIR), magnesium, dietary fiber, total sugar, caffeine, diabetes history, and heart disease history. Five machine learning models (Random Forest, XGBoost, LightGBM, Decision Tree, and KNN) were then constructed, and their performance in the testing set was comprehensively evaluated based on discrimination (AUC, AUPRC), calibration (ECE), and clinical net benefit (decision curve analysis [DCA]). SHAP (SHapley Additive exPlanations) analysis was subsequently performed to interpret the optimal model. Baseline characteristics indicated that individuals with edentulism exhibited a pattern of "advanced age - low socioeconomic status - insufficient dietary antioxidant intake - accumulation of chronic conditions." Restricted cubic splines (RCS) showed significant nonlinear protective associations of dietary fiber and magnesium intake with edentulism risk, whereas total sugar intake demonstrated a nonlinear positive association. Among all models, gradient boosting algorithms (XGBoost, LightGBM) achieved the highest discrimination (AUC = 0.855). Considering discrimination, reliability of predicted probabilities (ECE = 0.0097), and clinical net benefit, Random Forest was ultimately selected as the optimal model. SHAP analysis revealed that age, years of education, smoking status, and PIR were the most influential predictors of edentulism risk. This study successfully developed a Random Forest-based prediction model for edentulism risk, demonstrating strong discriminative performance, reliable calibration, and substantial clinical net benefit. Age, socioeconomic factors, and smoking status were identified as core risk determinants, while inadequate magnesium and dietary fiber intake emerged as key nutritional intervention targets. The model provides a useful decision-support tool for early screening and precision nutrition strategies among high-risk populations.

PMID 43012818
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PubMedBrain research bulletin2026-11-10

A single post-stress dose of caffeine preserves threat-safety discrimination but not fear extinction in rats exposed to single prolonged stress.

Lin Chen-Cheng CC, Chen Chieh-Yi CY, Chen Yu-Wen YW, Cheng Yu-Yen YY et al.

Post-traumatic stress disorder (PTSD) is characterized by impaired fear extinction and fear overgeneralization, yet no early pharmacological intervention has been established. Because the pathophysiology of PTSD develops over a modifiable period after trauma, we tested whether a single moderate dose of caffeine (30mg/kg) administered immediately after single prolonged stress (SPS) protects fear regulation and its underlying neurochemistry in male rats. The abilities of threat-safety discrimination and fear extinction were assessed using a Pavlovian discriminative fear conditioning paradigm, and tissue levels of serotonin (5-HT), dopamine (DA), norepinephrine (NE), and neuropeptide Y (NPY) were quantified in the hippocampus, medial prefrontal cortex (mPFC), and amygdala. The results demonstrated that caffeine produced a behavioral dissociation: it restored threat-safety discrimination but did not rescue the extinction retention deficits. This selectivity was mirrored neurochemically. Caffeine restored SPS-induced reductions in hippocampal 5-HT and DA and in mPFC NPY, but did not restore hippocampal NE or mPFC monoamines, and no changes were detected in the amygdala. These findings suggest that a single post-stress dose of caffeine acts through region-specific neurochemical pathways rather than providing global protection. Therefore, caffeine emerges as a promising and accessible candidate for early post-stress intervention targeting fear overgeneralization.

PMID 43008979
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