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Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs.
Pharm Res. 2000 Aug; 17(8):978-84.PR

Abstract

PURPOSE

To study the utility of the nasal route for the systemic delivery of L-dopa using water soluble prodrugs of L-dopa and to examine if this delivery method will result in preferential delivery to the CNS.

METHODS

Several alkyl ester prodrugs of L-dopa were prepared and their physicochemical properties were determined. In vitro hydrolysis rate constants in buffer, rat plasma, rat brain homogenate, rat CSF, and rat nasal berfusate were determined by HPLC. In vivo nasal experiments were carried out in rats. Levels of L-dopa and dopamine in plasma, CSF, and olfactory bulb were determined using HPLC method with electrochemical detection.

RESULTS

All the prodrugs showed improved solubility and lipophilicity with relatively fast in vitro conversion in rat plasma. Absorption was fast following nasal delivery of the prodrugs with bioavailability around 90%. Dopamine plasma levels did not change significantly following nasal administration of the butyl ester prodrug. Olfactory bulb and CSF L-dopa concentration were higher following nasal delivery of the butyl ester prodrug compared to an equivalent intravenous dose.

CONCLUSIONS

Utilization of water soluble prodrugs of L-dopa via the nasal route in the treatment of Parkinson's disease may have therapeutic advantages such as improved bioavailability, decreased side effects, and potentially enhanced CNS delivery.

Authors+Show Affiliations

Endo Pharmaceuticals, Garden City, New York 11530, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

11028945

Citation

Kao, H D., et al. "Enhancement of the Systemic and CNS Specific Delivery of L-dopa By the Nasal Administration of Its Water Soluble Prodrugs." Pharmaceutical Research, vol. 17, no. 8, 2000, pp. 978-84.
Kao HD, Traboulsi A, Itoh S, et al. Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs. Pharm Res. 2000;17(8):978-84.
Kao, H. D., Traboulsi, A., Itoh, S., Dittert, L., & Hussain, A. (2000). Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs. Pharmaceutical Research, 17(8), 978-84.
Kao HD, et al. Enhancement of the Systemic and CNS Specific Delivery of L-dopa By the Nasal Administration of Its Water Soluble Prodrugs. Pharm Res. 2000;17(8):978-84. PubMed PMID: 11028945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs. AU - Kao,H D, AU - Traboulsi,A, AU - Itoh,S, AU - Dittert,L, AU - Hussain,A, PY - 2000/10/12/pubmed PY - 2001/3/3/medline PY - 2000/10/12/entrez SP - 978 EP - 84 JF - Pharmaceutical research JO - Pharm Res VL - 17 IS - 8 N2 - PURPOSE: To study the utility of the nasal route for the systemic delivery of L-dopa using water soluble prodrugs of L-dopa and to examine if this delivery method will result in preferential delivery to the CNS. METHODS: Several alkyl ester prodrugs of L-dopa were prepared and their physicochemical properties were determined. In vitro hydrolysis rate constants in buffer, rat plasma, rat brain homogenate, rat CSF, and rat nasal berfusate were determined by HPLC. In vivo nasal experiments were carried out in rats. Levels of L-dopa and dopamine in plasma, CSF, and olfactory bulb were determined using HPLC method with electrochemical detection. RESULTS: All the prodrugs showed improved solubility and lipophilicity with relatively fast in vitro conversion in rat plasma. Absorption was fast following nasal delivery of the prodrugs with bioavailability around 90%. Dopamine plasma levels did not change significantly following nasal administration of the butyl ester prodrug. Olfactory bulb and CSF L-dopa concentration were higher following nasal delivery of the butyl ester prodrug compared to an equivalent intravenous dose. CONCLUSIONS: Utilization of water soluble prodrugs of L-dopa via the nasal route in the treatment of Parkinson's disease may have therapeutic advantages such as improved bioavailability, decreased side effects, and potentially enhanced CNS delivery. SN - 0724-8741 UR - https://www.unboundmedicine.com/medline/citation/11028945/Enhancement_of_the_systemic_and_CNS_specific_delivery_of_L_dopa_by_the_nasal_administration_of_its_water_soluble_prodrugs_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11028945.ui DB - PRIME DP - Unbound Medicine ER -