Apply to publish on medrx.eu
You are here: MedRX › All Topics
2 of 2 results
1.

Nasal Melatonin vs Oral Tablets: Why the Nose Has a Pharmacokinetic Edge

Marten O.

MedRX Res Notes. 2026 Aug 22:1–12. Free full text Review

Abstract

Melatonin is not a conventional sedative but a timing signal that tells the brain night has begun, which makes delivery unusually important. Oral tablets undergo extensive first-pass metabolism (absolute bioavailability ~15%; range 9–33%) and reach peak plasma concentrations only after 40–90 minutes. Intranasal delivery bypasses the gastrointestinal tract: human studies show peak plasma concentrations within ~5–10 minutes at doses of 200–400 µg, with exposure comparable to a 2.5 mg oral tablet. The earliest intranasal spray dissolved melatonin in ethanol and caused painful nasal irritation; modern alcohol-free hydroxypropyl-β-cyclodextrin systems solve solubility without the same tolerability problem. Intranasal melatonin remains investigational.

Keywords: Melatonin/administration & dosage Administration, Intranasal Biological Availability Cyclodextrins/chemistry

Full text → Similar articles

Key references

  1. DeMuro RL, et al. J Clin Pharmacol. 2000. PMID: 10883420
  2. Harpsøe NG, et al. Clin Pharmacokinet. 2015. PMID: 26008214
  3. Helfrich et al. Randomized crossover trial, intranasal melatonin. 2002. Free full text
  4. Vollrath L, Semm P, Gammel G. Intranasal melatonin sleep study. 1981. PDF
  5. Babu RJ, et al. Cyclodextrin-enhanced intranasal permeation. 2008. PubMed
  6. Merkus FWHM, et al. Intranasal melatonin formulation. US6007834A. Patent
2.

Nasal Creatine vs Oral Tablets: Why Direct Brain Delivery Could Offer a Cognitive Edge

Marten O.

MedRX Res Notes. 2026 Aug 25:1–13. Free full text Review

Abstract

Creatine and phosphocreatine buffer ATP in the brain, supporting working memory, long-term memory formation and reasoning under metabolic stress; meta-analyses of oral supplementation show memory improvements (SMD ~0.3), strongest in older adults and under hypoxia or sleep deprivation. Brain uptake from the bloodstream depends on the near-saturated SLC6A8 transporter at the blood-brain barrier, making brain creatine elevation slow and limited even at high oral doses. Intranasal delivery bypasses this gate via olfactory and trigeminal pathways: rat studies show higher creatine in olfactory bulbs, prefrontal cortex and hippocampus versus oral dosing, with fewer Barnes maze errors and better probe performance, and microparticle formulations further enhance uptake. Modeling suggests tens to low hundreds of milligrams nasally may match the brain availability of gram-scale oral doses. No human intranasal trials exist yet; the route remains experimental.

Keywords: Creatine/pharmacology Administration, Intranasal Blood-Brain Barrier/metabolism Phosphocreatine

Full text → Similar articles

Key references

  1. Gordji-Nejad A, et al. Single dose creatine improves cognitive performance during sleep deprivation. Sci Rep. 2024. PMID: 38321010
  2. Avgerinos KI, et al. Effects of creatine supplementation on cognitive function of healthy individuals. Exp Gerontol. 2018. PMID: 29704837
  3. Roschel H, et al. Creatine Supplementation and Brain Health. Nutrients. 2021. PMID: 33578976
  4. Intranasal creatine administration increases brain creatine level and improves spatial memory (rat study). PubMed search
  5. Intranasal microparticle delivery enhances brain creatine uptake. PubMed search
  6. Estimating the dosage and feasibility of intranasal administration of creatine. PubMed search
  7. EFSA. Creatine and improvement in cognitive function: health claim evaluation (Alzchem application). Scholar

No results were found.
Adjust your search term or clear the active filters.