Clinical trial evaluating apomorphine oromucosal solution in Parkinson's disease patients.

Apomorphine, used to treat OFF episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal solution could offer a non-invasive and user-friendly alternative. This two-part clinical study evaluated the safety, tolerability, pharmacokinetics (PK), and dose proportionality of a novel apomorphine hydrochloride oromucosal solution, as well as its relative bioavailability to subcutaneous apomorphine injection and apomorphine sublingual film.

Can nasal drug delivery bypass the blood-brain barrier?: questioning the direct transport theory.

The connection between the nasal cavity and the CNS by the olfactory neurones has been investigated extensively during the last decades with regard to its feasibility to serve as a direct drug transport route to the CSF and brain. This drug transport route has gained much interest as it may circumvent the blood-brain barrier (BBB), which prevents some drugs from entering the brain. Approximately 100 published papers mainly reporting animal experiments were reviewed to evaluate whether the experimental design used and the results generated provided adequate pharmacokinetic information to assess whether the investigated drug was transported directly from the olfactory area to the CNS.

Uptake of fluorescein isothiocyanate-labelled dextran into the CSF after intranasal and intravenous administration to rats.

With the growing number of patients suffering from central nervous system (CNS) diseases a suitable approach for drug targeting to the brain becomes more and more important. In the present study, the contribution of the nose-CSF pathway to the uptake of the model drug fluorescein isothiocyanate-labelled dextran with a molecular weight of 3.0 kDa (FD3) into the CSF was determined in rats.

Uptake of estradiol or progesterone into the CSF following intranasal and intravenous delivery in rats.

The uptake of estradiol and progesterone into the cerebrospinal fluid (CSF) after intranasal and intravenous administration in rats was investigated. Each animal received estradiol intranasally (40 microg/rat) and by intravenous infusion (10 microg/rat) into the jugular vein using a vascular access port. Hereafter, the same set of rats was treated with progesterone intranasally (200 microg/rat) and by intravenous infusion (104 microg/rat).

Uptake of melatonin into the cerebrospinal fluid after nasal and intravenous delivery: studies in rats and comparison with a human study.

Purpose: To investigate the possibility of direct transport of melatonin from the nasal cavity into the cerebrospinal fluid (CSF) after nasal administration in rats and to compare the animal results with a human study.

Methods: Rats (n = 8) were given melatonin both intranasally in one nostril (40 microg/rat) and intravenously by bolus injection (40 microg/rat) into the jugular vein using a Vascular Access Port. Just before and after drug administration, blood and CSF samples were taken and analyzed by HPLC.

Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous delivery in rats and humans.

The possibility of direct transport of hydroxocobalamin from the nasal cavity into the cerebrospinal fluid (CSF) after nasal administration in rats was investigated and the results were compared with a human study. Hydroxocobalamin was given to rats (n=8) both intranasally (214 microg/rat) and intravenously (49.5 microg/rat) into the jugular vein using a Vascular Access Port (VAP).

Direct access of drugs to the human brain after intranasal drug administration?

It has been suggested that intranasal (IN) drug delivery could be used to administer drugs directly to the brain, bypassing the blood-brain barrier. Conclusive evidence of this proposed route of drug transport has not been observed by IN-IV comparison. In eight neurosurgery patients with a CSF drain, the uptake in CSF and plasma after IN and IV drug administration was compared.

Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the nasal cavity.

Drug transport from the nasal cavity to the brain has gained much interest in the last decade. In the present study, a model was developed to determine the uptake of drugs into the cerebrospinal fluid (CSF) after nasal delivery in rats. CSF samples were taken using a cisternal puncture method.