Absorption: According to SwissADME (fig, 2), gabapentin follows Lipinski's and Egan's rule as

gabapentin has a low molecular weight of 171.24 g/mol, TPSA Value of 63.32 Ų and optimal
lipophilicity (Consensus Log Po/w) value of 0.79 which indicates that gabapentin can be easily
absorbed [1]. the absorption of gabapentin is influenced by its pKa value, which is a measure of
the acidity of the drug. The pKa of gabapentin is approximately 3.7. This means that at a pH
lower than 3.7, gabapentin exists mostly in its acidic form, while at a pH higher than 3.7, it exists
mostly in its basic form.
In the stomach, which has a pH of around 1.5-3.5, gabapentin is predominantly in its acidic form,
which limits its absorption. However, in the small intestine, which has a higher pH of around 5-
7, gabapentin is predominantly in its basic form, which enhances its absorption. Gabapentin has
2 hydrogen bond donors and 3 hydrogen bond acceptors, and log S (Ali) value of 0.26(fig,2).
which predicts gabapentin to be polar and highly soluble in water and other polar solvents
suggesting that gabapentin can easily absorbed by gastrointestinal (Gl) tract, The graphical
representation of gabapentin BOILED Egg (fig. 1) indicates that it lies within the yolk region
which suggests that gabapentin has a high probability to cross blood-brain barrier [2]. The value
of Log Kp (skin permeation) is -8.13 cm/s (fig. 2) indicating that gabapentin has low skin
permeability. Overall, all the molecular descriptors and parameters of bioavailability radar
predicts gabapentin has a low GI absorption. This means that a significant portion of the dose
may not be absorbed and instead may be excreted in the urine.

Distribution: Based on our Swiss model prediction for Gabapentin, The blood-brain barrier
(BBB) is projected to respond favorably to gabapentin, which means that Gabapentin could pass
through and enter the brain.[5] According to research by Feras I. Kanaze, Gabapentin readily
cross the BBB and accumulates in brain tissue through a process of active transport thought to be
system-L, which supports our findings from swiss prediction model.[1]
In addition based on the swiss model prediction, our drug is inside the yellow portion of boiled
egg,meaning it can crosses the BBB.[Figure1] Regarding the volume distribution and protein
binding of gabapentin, the Swiss model offers no details. However, a study suggest volume of
distribution of gabapentin is approximately 0.8L/kg in healthy adults. This indicates that
gabapentin is widely distributed throughout the body after administration, there is no binding of
plasma proteins by Gabapentin, LAT-1 actively carries them across the blood-brain barrier.[2]
Gabapentin is represented as a red dot in the Swiss model (Figure 1), showing that it is neither a
substrate of P-glycoprotein nor is it removed from the central nervous system by P-glycoprotein
[3].
A research article by Crowe, A., & Teoh, also suggest that Gabapentin has no effect on P-
Glycoprotein inhibition.[4]

Excretion: According to literature, Gabapentin is eliminated from the systemic circulation by

renal excretion as unchanged drug a Gabapentin is not appreciably metabolized in humans.
Gabapentin elimination half-life is 5 to 7 hours and is unaltered by dose or following multiple
dosing. [1]
Gabapentin has a relatively low degree of protein binding, with approximately 3% to 4% of the
drug being bound to plasma proteins. This suggests that protein binding is unlikely to have a
significant impact on the drug's excretion.
Gabapentin’s apparent total clearance is 100 mL/min in adults with normal renal function [2]
According to literature Peak plasma levels (Cmax) of gabapentin of 2.7–2.99 mg. l−1 are
achieved 3–3.2 h after ingestion of a single 300-mg capsule [7, 10]. As a result of the dose-
dependent saturable absorption of gabapentin, Cmax increases less than threefold when the dose
is tripled from 300 to 900 mg. [3]
According to Swiss ADME, Gabapentin is a highly water-soluble compound with a low
molecular weight (171.24 g/mol), which indicates renal excretion.
In pharmacology, the area under the plot of plasma concentration of a drug versus time after
dosage (called “area under the curve” or AUC) gives insight into the extent of exposure to a drug
and its clearance rate from the body[4]
[1]
https://www.ncbi.nlm.nih.gov/books/NBK493228/#:~:text=The%20elimination%20half%2Dlife
%20of,renally%2C%20with%20no%20active%20metabolites.

[2]Raouf, M., Atkinson, T. J., Crumb, M. W., & Fudin, J. (2017). Rational dosing of
gabapentin and pregabalin in chronic kidney disease. Journal of pain research, 10, 275–
278. https://doi.org/10.2147/JPR.S130942

[3] Rose, M., & Kam, P. (2002). Gabapentin: pharmacology and its use in pain
management. Anaesthesia, 57(5), 451–462. https://doi.org/10.1046/j.0003-
2409.2001.02399.x

[4] Scheff, J. D., Almon, R. R., Dubois, D. C., Jusko, W. J., & Androulakis, I. P. (2011).
Assessment of pharmacologic area under the curve when baselines are variable.
Pharmaceutical research, 28(5), 1081–1089. https://doi.org/10.1007/s11095-010-0363-8

https://pubmed.ncbi.nlm.nih.gov/22946876/
Chen, C., Cowles, V. E., & Sweeney, M. (2013). The intestinal absorption mechanism of
gabapentin makes it appropriate for gastroretentive delivery. Current clinical pharmacology, 8(1),
67–72.

[1] Arnott, J. L., & Planey, S. L. (2012, September 25). The influence of lipophilicity in drug
discovery and design. Expert Opinion on Drug Discovery; Informa.
https://doi.org/10.1517/17460441.2012.714363

[2] Yasaei R, Katta S, Saadabadi A. Gabapentin. [Updated 2022 Dec 19]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK493228/