Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Experiments
2.2. Data Handling
2.3. Pharmacokinetic Model Building
3. Results
3.1. Per Os Administration
3.2. Intranasal Administration
3.3. Combined Model
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Per Os Blood Data | |||
---|---|---|---|
Parameter | Estimated Value | SE | %RSE |
k12 (1/min) | 0.064 | 0.004 | 6.43% |
k23 (1/min) | 0.032 | 0.003 | 9.78% |
K32 (1/min) | 0.012 | 0.003 | 23.64% |
k20 (1/min) | 0.024 | 0.001 | 5.61% |
Vblood (L) | 0.279 | 0.014 | 5.16% |
Per Os—Mean Data | |||
---|---|---|---|
Parameter | Estimated value | SE | %RSE |
k12 (1/min) | 0.059 | 0.002 | 3.33% |
k20 (1/min) | 0.012 | 0.001 | 6.88% |
k23 (1/min) | 0.014 | 0.001 | 5.99% |
k24 (1/min) | 0.034 | 0.005 | 13.24% |
k42 (1/min) | 0.011 | 0.002 | 20.93% |
k30 (1/min) | 0.325 | 0.068 | 21.02% |
Vbrain (L) | 0.018 | 0.003 | 16.57% |
Per Os—Raw Data | |||
Parameter | Estimated value | SE | %RSE |
k12 (1/min) | 0.065 | 0.013 | 20.37% |
k20 (1/min) | 0.017 | 0.004 | 22.64% |
k23 (1/min) | 0.008 | 0.002 | 19.24% |
k24 (1/min) | 0.036 | 0.01 | 28.30% |
k42 (1/min) | 0.01 | 0.006 | 61.73% |
k30 (1/min) | 0.369 | 0.219 | 59.35% |
Vbrain (L) | 0.009 | 0.004 | 45.94% |
Per Os—Mean Data | |||
Parameter | Estimated value | SE | %RSE |
b1 | 0.012 | 0.004 | 32.02% |
b2 | 0.062 | 0.039 | 62.93% |
Per Os—RawData | |||
Parameter | Estimated Value | SE | %RSE |
a1 | 0.016 | 0.005 | 28.48% |
a2 | 0.004 | 0.001 | 31.09% |
IN—Mean Data | |||
---|---|---|---|
Parameter | Estimated Value | SE | %RSE |
Tlag (min) | 4.06 | 0.465 | 11.45% |
Tk0 (min) | 11.3 | 3.54 | 31.33% |
Mtt (min) | 56 | 1.01 | 1.80% |
ktr (1/min) | 0.171 | 0.0176 | 10.29% |
V1 | 0.021 | 0.0119 | 56.40% |
V2 | 0.005 | 0.0008 | 16.33% |
P1 | 0.543 | 0.131 | 24.13% |
P2 | 0.3 | 0.115 | 38.33% |
ka (1/min) | 0.173 | 0.0146 | 8.44% |
k20 (1/min) | 0.046 | 0.0229 | 49.78% |
IN—Raw Data | |||
Parameter | Estimated Value | SE | %RSE |
Tlag (min) | 3.72 | 0.371 | 9.97% |
Tk0 (min) | 11.6 | 4.47 | 38.53% |
Mtt (min) | 60.9 | 2.4 | 3.94% |
ktr (1/min) | 0.183 | 0.025 | 13.50% |
V1 | 0.027 | 0.015 | 55.15% |
V2 | 0.003 | 0.001 | 19.28% |
P1 | 0.683 | 0.074 | 10.85% |
P2 | 0.276 | 0.108 | 39.13% |
ka (1/min) | 0.566 | 0.128 | 22.61% |
k20 (1/min) | 0.05 | 0.021 | 42.69% |
Per Os—Mean Data | |||
Parameter | Estimated Value | SE | %RSE |
a1 | 0.016 | 0.006 | 39.81% |
b2 | 0.043 | 0.035 | 80.47% |
Per Os—Raw Data | |||
Parameter | Estimated Value | SE | %RSE |
a1 | 0.082 | 0.022 | 26.09% |
b2 | 0.238 | 0.058 | 24.41% |
Total Fit—Per Os and IN Raw Data | |||
---|---|---|---|
Parameter | Estimated Value | SE | % RSE |
k12 (1/min) | 0.065 | 0.013 | 19.79% |
k20 (1/min) | 0.039 | 0.009 | 23.66% |
k23 (1/min) | 0.011 | 0.008 | 70.55% |
k24 (1/min) | 0.018 | 0.022 | 119.67% |
k42 (1/min) | 0.031 | 0.018 | 59.03% |
k30 (1/min) | 0.276 | 0.093 | 33.80% |
Vbrain_PO (L) | 0.015 | 0.008 | 51.43% |
Tlag (min) | 3.59 | 0.004 | 0.11% |
Tk0 (min) | 11.4 | 0.007 | 0.06% |
Mtt (min) | 53.8 | 8.51 | 15.82% |
ktr (1/min) | 0.205 | 0.088 | 43.12% |
Vblood_IN (L) | 0.024 | 0.003 | 12.46% |
Vbrain_IN (L) | 0.005 | 0.001 | 22.85% |
P1 | 0.557 | 0.055 | 9.95% |
P2 | 0.306 | 0.057 | 18.59% |
ka (1/min) | 0.127 | 0.131 | 103.15% |
Total Fit—Per Os and IN Raw data | |||
Parameter | Estimated Value | SE | % RSE |
a1 | 0.017 | 0.005 | 28.32% |
a2 | 0.004 | 0.001 | 30.50% |
a3 | 0.084 | 0.022 | 25.66% |
b1 | 0.236 | 0.057 | 24.24% |
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Kaikousidis, C.; Papakyriakopoulou, P.; Dokoumetzidis, A.; Valsami, G. Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice. Pharmaceutics 2023, 15, 1409. https://doi.org/10.3390/pharmaceutics15051409
Kaikousidis C, Papakyriakopoulou P, Dokoumetzidis A, Valsami G. Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice. Pharmaceutics. 2023; 15(5):1409. https://doi.org/10.3390/pharmaceutics15051409
Chicago/Turabian StyleKaikousidis, Christos, Paraskevi Papakyriakopoulou, Aristides Dokoumetzidis, and Georgia Valsami. 2023. "Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice" Pharmaceutics 15, no. 5: 1409. https://doi.org/10.3390/pharmaceutics15051409