Pharmacokinetics of Nanosomal Form of Levodopa in Intranasal Administration

Andrey Anatolievich Nedorubov; Alexey Nikitich Pavlov; Natalia Valeryevna Pyatigorskaya; Galina Eduardovna Brkich; Marina Maksimovna Shabalina

doi:10.3889/oamjms.2019.749

Authors

Andrey Anatolievich Nedorubov Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, Trubetskaya Street, 8, Moscow, Russian Federation
Alexey Nikitich Pavlov Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, Trubetskaya Street, 8, Moscow, Russian Federation
Natalia Valeryevna Pyatigorskaya Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, Trubetskaya Street, 8, Moscow, Russian Federation
Galina Eduardovna Brkich Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, Trubetskaya Street, 8, Moscow, Russian Federation
Marina Maksimovna Shabalina Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, Trubetskaya Street, 8, Moscow, Russian Federation

DOI:

https://doi.org/10.3889/oamjms.2019.749

Keywords:

levodopa, intranasal administration, Parkinson's disease, pharmacokinetics, HPLC-MS/MS

Abstract

BACKGROUND: Parkinson's disease is one of the most common neurological diseases. Pathogenesis of the disease is associated with destruction and death of neurons that produce the neurotransmitter dopamine. The precursor to dopamine, which crosses the protective blood-brain barrier, is the amino acid 3, 4-dihydroxy-L-phenylalanine â€“ levodopa, L-DOPA. The investigational drug is a pharmaceutical composition, containing L-DOPA as an active substance, which is distributed in a polymer matrix based on a biodegradable copolymer of lactic/glycolic acids.

AIM: This work aimed to study the main pharmacokinetic parameters for the drug "L-DOPA â€“ PC, nasal drops" and comparator drugs "L-DOPA in oil", "L-DOPA â€“ PC in purified water", reference product â€“ tablets "Madopar 125".

METHODS: To increase the bioavailability of the active substance L-DOPA, a new route of administration was used for the first time â€“ nasal administration. Pharmacokinetics of the innovative drug with the intranasal route of administration was investigated in rabbits. The L-DOPA concentration in blood plasma was determined by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS).

RESULTS: Bioavailability of the drug â€“ nasal drops were 244.4% compared with the drug "Madopar 125".

CONCLUSION: Assay procedure for the determination of L-DOPA in animal blood plasma using liquid chromatography with tandem mass-selective detection (HPLC-MS/MS) was developed and validated.