Objective: To determine the pharmacokinetic (PK) profile of amantadine in the common marmoset (Callithrix jacchus).

Background: Amantadine is currently approved for the treatment of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia by the United States Food and Drug Administration. Amantadine was shown to reduce dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmoset, yet the administered doses varied considerably in terms of range (from 0.01 to 10 mg/kg), resulting in variable and undetermined plasma exposure. Here, we sought to determine plasma exposure following administration of amantadine to marmosets. We selected 3 doses of amantadine, 0.1, 1 and 10 mg/kg, to characterise the PK parameters of doses previously used in this species.

Method: Six marmosets were administered amantadine 0.1, 1 and 10 mg/kg sub-cutaneously (s.c.), as well as 1 mg/kg intra-venously (i.v.). Serial blood samples were collected, plasma was harvested and analysed by ultra high-performance liquid chromatography coupled with heat assisted electrospray ionisation mass spectrometry (UHPLC-HESI-MS/MS). Amantadine PK parameters were determined by non-compartmental analysis.

Results: Preliminary analysis indicates that, after s.c. administration of amantadine 1 mg/kg, maximal plasma concentration (C_max) was 112.6 ng/mL. Time to C_max (T_max) approximated 240 min, while half-life (T_1/2) was 7 h. Area under the curve 0-t (AUC_0-t) was 1,608 ng/mL·h.

Conclusion: Our early results detail the plasma exposure of amantadine after administration of the dose of 1 mg/kg s.c. in the marmoset. These results should be informative in the design of pre-clinical studies in this species. Analysis is currently on-going with amantadine 0.1 and 10 mg/kg s.c., as well as amantadine 1 mg/kg i.v., and will provide a more comprehensive picture of the PK of amantadine in the marmoset.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/characterisation-of-the-pharmacokinetic-profile-of-amantadine-in-the-common-marmoset/