Sure, technically, but read the FDA paper on it's pharmacokinetics.
Smoking, shooting, or squirting it up your ass won't do the trick. But injecting it would put it in direct contact with red blood cells, and so would rectal administration via absorption through rectal mucosa.
Lisdexamfetamine needs to pass through the GI tract where there's proper enzymatic activity.
"The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effect."
"Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. .... LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon"
"The intact prodrug, LDX, was readily absorbed from the GI tract after oral administration, with relatively high levels of LDX detected in the portal blood of rats. When LDX was perfused into isolated segments of rat duodenum, jejunum, and ileum, it was absorbed into the systemic circulation; however, LDX was not absorbed during perfusion into colonic segments. These findings indicate that absorption of LDX occurs via carrier-mediated transport in the small intestines and are consistent with the physicochemical properties of LDX (ie, high aqueous solubility of greater than 0.85 g/mL within the physiologically relevant pH range of 1 to 812 and low lipophilicity [logP–1.75, unpublished data]), which would predict poor passive diffusion across biologic membranes"
But hey, here I am arguing on my weekend about why exactly putting a certain amphetamine prodrug up your ass won't work. What are we doing with our lives?
Ah - I understand these passages such that they describe the passage of the intact LDX molecule into the bloodstream, and I don't see mention of the lysine-amphetamine cleavage action. This describes what part of the intestine is able to pull the whole LDX molecule into the blood. Note the distinction between absorption and metabolism. Later passages:
LDX was not metabolized in vitro by SGF, SIF, or trypsin, [so] any conversion of LDX to d-amphetamine in the GI tract in vivo is likely to be minimal. [...,] consistent with a model of absorption of predominantly intact LDX with subsequent enzymatic conversion to active d-amphetamine and l-lysine.
LDX was metabolized to d-amphetamine in rat and human whole blood but not in plasma. [Red blood cells] are responsible for the presystemic conversion of LDX to d-amphetamine.
LDX was metabolized to d-amphetamine by human RBCs but not by other blood fractions, such as white blood cells or platelets. Moreover, RBCs had a very high capacity for the metabolism of LDX. The rate of metabolism was not substantially reduced until concentrations of RBCs were reduced to 10% of normal hematocrit. Lysis of the RBCs also had little impact on the rate of metabolism of LDX, and nor did EDTA (a calcium chelator that inhibits the activity of calcium-dependent enzymes).
In conclusion, LDX is absorbed as the intact prodrug and converted to inactive l-lysine and active d-amphetamine primarily in the blood by RBCs.
Smoking, shooting, or squirting it up your ass won't do the trick. But injecting it would put it in direct contact with red blood cells, and so would rectal administration via absorption through rectal mucosa.
Lisdexamfetamine needs to pass through the GI tract where there's proper enzymatic activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805701/
"The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effect."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898170/
"Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. .... LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon"
"The intact prodrug, LDX, was readily absorbed from the GI tract after oral administration, with relatively high levels of LDX detected in the portal blood of rats. When LDX was perfused into isolated segments of rat duodenum, jejunum, and ileum, it was absorbed into the systemic circulation; however, LDX was not absorbed during perfusion into colonic segments. These findings indicate that absorption of LDX occurs via carrier-mediated transport in the small intestines and are consistent with the physicochemical properties of LDX (ie, high aqueous solubility of greater than 0.85 g/mL within the physiologically relevant pH range of 1 to 812 and low lipophilicity [logP–1.75, unpublished data]), which would predict poor passive diffusion across biologic membranes"
But hey, here I am arguing on my weekend about why exactly putting a certain amphetamine prodrug up your ass won't work. What are we doing with our lives?