Transport of cephalexin to the cerebrospinal fluid directly from the nasal cavity

Abstract

The aim of the present study has been to confirm the existence of a transport pathway for a drug (cephalexin) to the cerebrospinal fluid (CSF) directly from the nasal cavity, by comparing the drug's concentrations in CSF after intranasal (i.n.), intravenous (i.v.) and intraduodenal (i.d.) administration. Higher levels of the drug were found in CSF following i.n. administration compared with the i.v. and i.d. routes, even though its plasma concentrations were similar. These findings suggest the existence of a direct transport pathway for cephalexin from the nasal cavity to the CSF. The concentration of drug in CSF at 15 min after i.n. administration was higher than that at 30 min. In contrast, its concentrations in CSF at 15 min after i.v. and i.d. administration were not significantly different from those at 30 min. The results confirm the presence of a direct transport pathway to CSF from the nasal cavity. This pathway may represent a new delivery route to CSF and possibly to brain parenchyma.

Is nose-to-brain transport of drugs in man a reality?

“…This has been shown among others for dihydroergotamine (Wang et al 1998), cocaine (Chow et al 1999), lidocaine (Chou & Donovan 1998) and cefalexin (Sakane et al 1991). The extracellular pathway, that transports polar drugs through tight junctions (see Epithelial cell barrier above) between sustentacular cells and olfactory neurons into the CSF, relies on a direct anatomic connection between the submucosa and the subarachnoid extensions, the perineural space surrounding the olfactory nerves, as they penetrate the cribriform plate ( Figure 6) (Jackson et al 1979).…”

Delivery of Nerve Growth Factor to the Brain via the Olfactory Pathway

“…CSF was obtained by cisternal puncture with a 23-gauge needle connected to polyethylene tubing. Collection was terminated as soon as any blood began to appear in the tubing (24).…”

“…This finding provides further evidence for a direct connection between the nose and the brain. A variety of substances, including metals (5,8), dyes (30), viruses (21), peptides (22,23), proteins (1,2,28) and drugs (4,24), have been reported to reach the brain from the nasal cavity, without having to cross the BBB.…”

Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery

“…It is also well-established that there exists a direct anatomical connection between the nasal cavity and the CNS by paracellular and transcellular pathway as well as through trigeminal neurons which suggest the scope of the development of CNS therapeutics for intranasal administration. Drugs such as sulfonamides (Sakane et al, 1991a), cephalexin (Sakane et al, 1991b), progesterone (Anand Kumar et al, 1982) and zidovudine (Seki et al, 1994) are reported to be successfully delivered to brain by intranasal route. Drugs presently in market such as estradiol for hormone replacement therapy, nicotine for smoking cessation, cyanocobalamin to treat vitamin B 12 deficiency, zolmitriptan and sumatriptan for migraine and cluster headache, buserelin for the treatment of prostate cancer, are other examples of intranasally administered drugs for systemic effect.…”