Pharmacokinetic Evaluation of Nalmefene PLGA Microspheres in Rats

Harish Kaushik KOTAKONDA*, ****, °, Malothu NAGULU**, Narasimha Reddy YELLU***°

* Dept of Pharmacy, Institute of Science and Technology, Jawaharlal Nehru Technological University, Hyderabad, India.
** Dept of Pharmacology, Swami Ramananda Tirtha Institute of Pharmaceutical Sciences, Nalgonda, India
*** Dept of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, India.
**** Dept of Drug Metabolism and Pharmacokinetics, JVR Biosciences, Hyderabad, India.

°Corresponding Author:
Email: yellu_nr@yahoo. com

Summary

Pharmacotherapies of insobriety is very limited till date. Few pharmacotherapies have been established as anti-craving drugs to reduce relapse risk or alcohol intake in alcoholism. The available bolus administration pharmacotherapy is also impeded by the higher rates of patient non-compliance, unwanted adverse reactions, and fluctuating drug levels. A long-term drug delivery system would help overcome upon these limitations. The purpose of this work was to perform comparative pharmacokinetic evaluation and define the appropriate dosage regimen of different extended release nalmefene loaded PLGA biodegradable microspheres formulations prepared by O/O emulsification solvent evaporation method for the treatment of alcoholism. MSA, MSB and MSC achieved peak plasma concentration of 105. 80 ± 15. 30 ng/mL, 164. 29 ± 32. 27 ng/mL and 262. 94 ± 48. 94 ng/mL in 72 hr, 12 hr and 12 hr, respectively and plasma concentrations sustained upto 720-1080 hr. The plasma exposure (AUClast) achieved by SC injection, IV injection, MSA, MSB and MSC nalmefene formulations are 442. 38 ± 64. 31, 613. 86 ± 75. 13, 57553. 28 ± 8320. 60, 48878. 81 ± 9603. 06 and 52805. 75 ± 9828. 14 hr. ng/mL, respectively. The optimum predicted dosing regimen for each of these formulations would be as 21-day, 7-day and 14-day dosing for MSA, MSB and MSC formulation, respectively. The results of the study demonstrated the feasibility of long term delivery of nalmefene using PLGA biodegradable microspheres by providing a relatively constant nalmefene plasma concentration for at least one to two months in rats.

Key Words :
Nalmefene, PLGA, Microspheres, Sustained Release, Pharmacokinetics, Formulation