Z. Karasova, J., Hrabinova, M., Krejciova, M., Jun, D., Kuca, K. (2019). Donepezil and rivastigmine: pharmacokinetics profile and brain-targeting after intramuscular application in rats. Iranian Journal of Pharmaceutical Research, (), -. doi: 10.22037/ijpr.2019.1100723
Jana Z. Karasova; Martina Hrabinova; Marketa Krejciova; Daniel Jun; Kamil Kuca. "Donepezil and rivastigmine: pharmacokinetics profile and brain-targeting after intramuscular application in rats". Iranian Journal of Pharmaceutical Research, , , 2019, -. doi: 10.22037/ijpr.2019.1100723
Z. Karasova, J., Hrabinova, M., Krejciova, M., Jun, D., Kuca, K. (2019). 'Donepezil and rivastigmine: pharmacokinetics profile and brain-targeting after intramuscular application in rats', Iranian Journal of Pharmaceutical Research, (), pp. -. doi: 10.22037/ijpr.2019.1100723
Z. Karasova, J., Hrabinova, M., Krejciova, M., Jun, D., Kuca, K. Donepezil and rivastigmine: pharmacokinetics profile and brain-targeting after intramuscular application in rats. Iranian Journal of Pharmaceutical Research, 2019; (): -. doi: 10.22037/ijpr.2019.1100723
Donepezil and rivastigmine: pharmacokinetics profile and brain-targeting after intramuscular application in rats
1Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic
2Biomedical Research Centre, University Hospital, Hradec Kralove, Czech Republic
3Department of Cellular Biology and Pharmacology, Florida International University, Miami, Florida, USA
Abstract
Current palliative pharmacotherapy of Alzheimer’s disease based on the cholinergic hypothesis led to the development of four cholinesterase inhibitors. These compounds can bring prolongation of the symptom-free period in some patients. This is the first report directly comparing donepezil and rivastigmine plasma and brain levels in in vivo study. Donepezil and rivastigmine were applied i.m. to rats; the dose was calculated from clinical recommendations. The samples were analysed on an Agilent 1260 Series LC with UV/VIS detector. An analytical column (Waters Spherisorb S5 W (250 mm × 4.6 i.d.; 5 μm particle size)) with guard column (Waters Spherisorb S5 W (30 mm × 4.6 mm i.d.)) was used. The mobile phase contained acetonitrile and 50 mM sodium dihydrogen phosphate (17:83; v/v); pH 3.1. The LLOQ in rat plasma was 0.5 ng/ml for donepezil and 0.8 ng/ml for rivastigmine, and the LLOQ in rat brain was 1.0 ng/ml for donepezil and 1.1 ng/ml for rivastigmine. Both compounds showed ability to target the central nervous system, with brain concentrations exceeding those in plasma. Maximum brain concentration after i.m. administration was reached in the 36 (8.34 ± 0.34 ng/ml) and 17 minute (6.18 ± 0.40 ng/ml) respectively for donepezil and rivastigmine. The differences in brain profile can be most easily expressed by plasma/brain AUCtotal ratios: donepezil ratio in the brain was nine-times higher than in plasma and rivastigmine ratio was less than two-times higher than in plasma.
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