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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

PubMedJournal of current ophthalmology2026-08-29

Caffeine Intake Effects on Intraocular Pressure in Healthy and Glaucomatous Populations: A Systematic Review and Meta-Analysis.

Simanjuntak Owen Paruhum OP, Jocelyn Olivia O, Simanjuntak Kevin Tadeus KT, Abidin Raniindra Khalisha Soediro RKS et al.

To evaluate the effect of caffeine intake on intraocular pressure (IOP). The PubMed, Cochrane, Scopus, and ProQuest databases were searched for publications of randomized trials investigating the effect of caffeine consumption on IOP in healthy and glaucomatous populations until February 1, 2025. Outcomes at 30 min, 1, 1.5, 2, and 3 h were analyzed using a random-effects model. Subgroup analysis was done for different types of caffeine-containing beverages and different amounts of caffeine. Sixteen studies, including 599 healthy participants and 63 glaucomatous patients (with primary open-angle glaucoma, ocular hypertension, and normotensive glaucoma), were included in this meta-analysis. The weighted mean difference (WMD) with 95% confidence intervals of IOP in the healthy population at 30 min, 1 h, 1.5 h, and 2 h were significant at 0.61 (0.07; 1.16), 0.87 (0.40; 1.33), 1.60 (0.40; 2.80), and 0.63 (0.03; 1.22), respectively. In glaucomatous patients, WMD at 1 and 1.5 h time points were significant at 1.51 (0.83; 2.18) and 1.39 (0.99; 1.78), respectively. Ingestion of >100 mg of caffeine significantly increased IOP at 30 min, 1, and 1.5 h, whereas ingestion of ≤100 mg did not significantly increase IOP in healthy populations. All included studies with glaucomatous populations used >100 mg of caffeine. Caffeine ingestion, especially of >100 mg, acutely elevates IOP in both healthy and glaucomatous populations.

PMID 42666870
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PubMedUltrasonics sonochemistry2026-08-29

Synergistic effects of ultrasound and yeast co-fermentation on microstructural, metabolic, and sensory properties of Robusta coffee.

Ni Jie J, Tang Huihua H, Tang Haoyuan H, Cao Cuihui C et al.

The study investigated an approach combining ultrasound with co-fermentation of P. fermentans and K. marxianus to improve the microstructural, metabolic, and sensory characteristics of Robusta coffee. Ultrasound treatment at 100, 200, and 300 W modified the surface microstructure of green coffee beans. Among them, 200 W exhibited the most pronounced promotion of yeast growth during fermentation (FU2). Compared with the control, the combined ultrasound and fermentation treatment increased total flavonoid and polyphenol contents while reducing caffeine and chlorogenic acid contents. In cupping tests, FU2 received the highest score (82.16 ± 0.58), noted for roasted, cocoa, floral, and honey aromas. Headspace solid-phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS) analysis showed reduced undesirable volatile compounds (VCs) (pyrazines, pyridines and phenolic volatiles) and increased furans, alcohols, and esters in fermented samples. Metabolomics revealed significant alterations in metabolite profiles after ultrasound treatment. These metabolic changes were further regulated during fermentation, accompanied by significant enrichment of flavor precursor pathways, including phenylalanine metabolism, pyruvate metabolism, and the citrate cycle. These findings provide a potential strategy for improving the sensory quality and value-added utilization of Robusta coffee.

PMID 42667730
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PubMedClinical pharmacokinetics2026-08-29

Effect of Rivoceranib 200 mg Once Daily on the Pharmacokinetics of a Cocktail Probe Substrate of Cytochrome P450 Enzymes: A Phase I Trial in Healthy Volunteers.

Nguyen David D, Wei Xiaohui Tracey XT, Meng Xianzhang X, Alexander Laura L et al.

Rivoceranib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor with antitumor activity, is metabolized in the liver mostly by cytochrome P450 (CYP)3A4/5. In vitro studies suggest that rivoceranib at clinically relevant concentrations may inhibit metabolism of various CYP substrates. This study evaluated the effects of rivoceranib 200 mg once daily (QD) on the pharmacokinetics of various CYP substrates using the Cooperstown 5+1 cocktail. The dosing regimen of rivoceranib used in this study is similar to the proposed rivoceranib regimen (250 mg QD) in combination with camrelizumab for the treatment of patients with hepatocellular carcinoma. This open-label, fixed-sequence, crossover, drug-drug interaction phase I study evaluated the impact of multiple oral doses of rivoceranib 200 mg QD on the single oral dose pharmacokinetics of CYP enzyme substrates administered in the modified Cooperstown 5+1 cocktail (caffeine 200 mg [CYP1A2], warfarin 10 mg [S-warfarin as CYP2C9 substrate] + vitamin K 10 mg, omeprazole 40 mg [CYP2C19], dextromethorphan 30 mg [CYP2D6], and midazolam 2 mg [CYP3A4]) in 18 healthy volunteers. After fasting, volunteers received a single dose of the Cooperstown 5+1 cocktail on day 1 and rivoceranib plus Cooperstown 5+1 cocktail on day 11. After completing a meal, volunteers received a single dose of rivoceranib on days 6-10 and 12-15. Blood samples for pharmcokinetic analyses of substrates were collected pre-dose and up to 120 h post-Cooperstown 5+1 cocktail dosing on days 1 and 11. Volunteers returned once between days 21 and 25 for safety follow-up. Rivoceranib 200 mg QD decreased the cumulative area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) for caffeine by 20% and maximum observed plasma concentration (Cmax) by 7%, increased S-warfarin AUC0-inf by 1.35-fold and Cmax by 1.05-fold, increased omeprazole AUC0-inf by 2.06-fold and Cmax by 1.64-fold, increased dextromethorphan AUC0-inf by 2.67-fold and Cmax by 1.9-fold, and increased midazolam AUC0-inf by 1.44-fold and Cmax by 1.15-fold. Rivoceranib 200 mg QD may substantially inhibit the metabolism of CYP2D6 substrates. Therefore, concomitant use of CYP2D6 substrate drugs with rivoceranib should be approached with caution, and dose adjustment of substrates of CYP2D6 may be necessary when co-administration cannot be avoided. Rivoceranib 200 mg QD may also exert weak inhibitory effects on the metabolism of CYP3A, CYP2C9, and CYP2C19 substrates. In such cases, close monitoring for substrate-related adverse reactions is recommended, particularly when toxicity is sensitive to increased exposures of these substrate drugs. ClinicalTrials.gov identifier: NCT03561298.

PMID 42667590
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PubMedJournal of nutrition and metabolism2026-08-28

Assessment of Chocolate, Cheese, and Caffeine as Migraine Triggers: A Systematic Review and Meta-Analysis of Patient-Reported Trigger Rates.

Alzahrani Hayat H

Migraine is a common neurological disorder affecting approximately 14%-15% of the global population and is a leading cause of years lived with disability. Dietary factors, including chocolate, caffeine, and cheese, are frequently reported as migraine triggers; however, their prevalence and contribution to migraine attacks remain inconsistent across studies. This systematic review and meta-analysis aimed to estimate the pooled prevalence of chocolate, caffeine, and cheese as patient-reported migraine triggers. This systematic review and meta-analysis was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and reported following the PRISMA 2020 Statement and MOOSE guidelines. A systematic search of PubMed, MEDLINE (via Ovid), Ovid, and Scopus was conducted from database inception to November 11, 2024. Observational studies reporting quantitative data on chocolate, caffeine, or cheese as migraine triggers were included. Data were synthesized using a random-effects meta-analysis of proportions in Jamovi (Version 2.3). Eight studies included, but seven only contributed to the quantitative meta-analysis. The pooled prevalence of patient-reported migraine triggers was 13.9% for chocolate (95% CI: 7.0%-21.0%), 8.0% for cheese (95% CI: 3.0%-12.0%), and 12.0% for caffeine (95% CI: 6.0%-19.0%) (all p < 0.001). Substantial heterogeneity was observed across all analyses (I2 > 95%). Four studies were rated as good quality and four as fair quality using the NHLBI Quality Assessment Tool. Chocolate, caffeine, and cheese are commonly reported migraine triggers; however, their effects vary considerably among individuals. Given the substantial heterogeneity and reliance on observational, self-reported data, routine avoidance of these foods cannot be universally recommended. Instead, individualized trigger identification, supported by headache diaries, should guide dietary management. Further well-designed prospective studies are needed to clarify causal relationships.

PMID 42662243
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PubMedThe Science of the total environment2026-08-28

Contaminant covariation as a potential indicator of hydrological connectivity in an urban canal-river system, Thailand.

Ziegler Alan D AD, Lee Theodora Hui Yian THY, Srinuansom Khajornkiat K, Boonta Teppitag T et al.

Urban canals frequently convey untreated wastewater to receiving rivers, but in the absence of flow data, tracing this contamination remains a major obstacle for regulatory agencies. To test whether contaminant-mixture structure can serve as a hydrological tracer, we conducted twelve monthly synoptic campaigns across nine stations in the Mae Kha Canal-Ping River system (northern Thailand). Canal stations exhibited a robust, covarying wastewater fingerprint-dominated by ace-sulfame, caffeine, and gemfibrozil-that was entirely absent from the upstream river. This canal signal decayed predictably downstream, yet several wastewater-exclusive compounds remained detectable in the river, confirming persistent urban influence despite substantial in-channel attenuation. Notably, atrazine followed a contrasting river-dominated pattern, demonstrating that external agricultural inputs modify-but do not erase-the canal-derived signature. Our findings introduce a practical, flow-independent framework: by analyzing the covariance of persistent and labile tracers, mixture composition can distinguish urban hydraulic connectivity from simple dilution, even in ungauged catchments. This approach offers regulatory bodies a low-cost diagnostic tool to prioritize canal interceptors and validate river-quality models where conventional monitoring infrastructure is sparse.

PMID 42664653
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PubMedCureus2026-08-28

Live Sextuplet Birth After Ovulation Induction in a Patient With Secondary Infertility: A Case Report.

Abdelgader Alla A, Daaoud Ibrahim I, Ali Dawelbait Azza Mohamed AM, Abuobida Baharelden B et al.

High-order multiple pregnancy is an unusual but serious complication of ovulation induction and is associated with significant maternal, fetal, and neonatal risks. While ovulation induction has been commonly used in the management of unexplained infertility, multifetal gestation remains an important iatrogenic outcome despite careful monitoring. In this article, we report a rare case of high-order multiple pregnancy following the induction of clomiphene citrate in a woman with unexplained secondary infertility. A 30-year-old para 1 female patient (eight years long) presented to Tadawi Medical Hospital, Khamis Mushait, Saudi Arabia, seeking pregnancy for secondary infertility. An infertility study confirmed normal hormonal status, bilateral tubal patency on hysterosalpingography, and normal semen analysis of her husband, and a diagnosis of unexplained secondary infertility was made. At the start of the stage, she underwent routine cycle monitoring using timing for intercourse and received folic acid, vitamins, and L-arginine. Induction of ovulation was accomplished by clomiphene citrate 50 mg daily for five days. On day 12, she had mild ovarian hyperstimulation, managed lightly. Initial early pregnancy evaluation showed markedly increased beta-human chorionic gonadotropin levels. Ultrasound revealed five gestational sacs that each harbored a viable fetal pole, pointing towards high-order multifetal gestation. The patient received close antenatal follow-up every two weeks. Fetal reduction was recommended due to the high maternal and perinatal risks; however, she declined. Cervical cerclage at 14 weeks gestation with Mersilene was performed because of the increased risk of cervical insufficiency. She was kept on progesterone support and was placed on dexamethasone for fetal lung maturation at 24 weeks. Serial ultrasounds revealed continuous viability of all fetuses and no gross structural anomalies. Although elective delivery was planned at 30-32 weeks, she developed preterm labor at 28 weeks and underwent cesarean section. Each neonate was born alive and placed in the neonatal intensive care unit for approximately five weeks. A rare situation with an extremely serious management challenge of high-order multiple pregnancy, including the complications post-ovulation induction and management challenges that this case presents. To facilitate these outcomes, it is critical that intensive monitoring, timely intervention, complex management, multidisciplinary effort, as well as neonatal support occur.

PMID 42662356
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