Editing Pseudoephedrine (section)

===Pharmacokinetics===
====Absorption====
Pseudoephedrine is [[oral administration|orally active]] and is readily [[absorption (pharmacokinetics)|absorbed]] from the [[gastrointestinal tract]].<ref name="GłowackaWiela-Hojeńska2021" /><ref name="Eccles2007" /> Its oral [[bioavailability]] is approximately 100%.<ref name="BruntonLazoParker2006" /> The drug reaches [[Cmax (pharmacology)|peak]] concentrations after 1 to 4{{nbsp}}hours (mean 1.9{{nbsp}}hours) in the case of the [[immediate-release]] formulation and after 2 to 6{{nbsp}}hours in the case of the [[extended-release]] formulation.<ref name="GłowackaWiela-Hojeńska2021" /><ref name="Eccles2007" /> The [[onset of action]] of pseudoephedrine is 30{{nbsp}}minutes.<ref name="GłowackaWiela-Hojeńska2021" />

====Distribution====
Pseudoephedrine, due to its lack of [[Chemical polarity|polar]] [[Phenols|phenolic]] [[functional group|group]]s, is relatively [[lipophilic]].<ref name="ChuaBenrimojTriggs1989" /> This is a property it shares with related sympathomimetic and decongestant agents like [[ephedrine]] and [[phenylpropanolamine]].<ref name="ChuaBenrimojTriggs1989" /> These agents are widely [[distribution (pharmacology)|distributed]] throughout the body and cross the [[blood–brain barrier]].<ref name="ChuaBenrimojTriggs1989" /> However, it is said that pseudoephedrine and phenylpropanolamine cross the blood-brain barrier only to some extent and that pseudoephedrine has limited [[central nervous system]] activity, suggesting that it is partially [[peripherally selective drug|peripherally selective]].<ref name="ODonnell1995" /><ref name="BouchardWeberGeiger2002" /> The blood-brain barrier permeability of pseudoephedrine, ephedrine, and phenylpropanolamine is reduced compared to other [[substituted amphetamine|amphetamines]] due to the presence of a [[hydroxyl group]] at the β carbon which decreases their [[lipophilicity]].<ref name="BouchardWeberGeiger2002">{{cite journal | vauthors = Bouchard R, Weber AR, Geiger JD | title = Informed decision-making on sympathomimetic use in sport and health | journal = Clin J Sport Med | volume = 12 | issue = 4 | pages = 209–224 | date = July 2002 | pmid = 12131054 | doi = 10.1097/00042752-200207000-00003 | url = }}</ref> As such, they have a greater ratio of peripheral cardiovascular to central psychostimulant effect.<ref name="BouchardWeberGeiger2002" /> Besides entering the brain, these substances also cross the [[placenta]] and enter [[breast milk]].<ref name="ChuaBenrimojTriggs1989" />

The [[plasma protein binding]] of pseudoephedrine has been reported to be approximately 21 to 29%.<ref name="VolppHolzgrabe2019" /><ref name="Schmidt2023" /> It is bound to [[orosomucoid|α<sub>1</sub>-acid glycoprotein]] (AGP) and [[human serum albumin|albumin]] (HSA).<ref name="VolppHolzgrabe2019" /><ref name="Schmidt2023" />

====Metabolism====
Pseudoephedrine is not extensively [[drug metabolism|metabolized]] and is subjected to minimal [[first-pass metabolism]] with oral administration.<ref name="ChuaBenrimojTriggs1989" /><ref name="GłowackaWiela-Hojeńska2021" /><ref name="Eccles2007" /> Due to its [[methyl group]] at the α [[carbon]] (i.e., it is an [[substituted amphetamine|amphetamine]]), pseudoephedrine is not a [[substrate (biochemistry)|substrate]] for [[monoamine oxidase]] (MAO) and is not metabolized by this [[enzyme]].<ref name="ODonnell1995" /><ref name="ChuaBenrimojTriggs1989" /><ref name="JohnsonHricik1993">{{cite journal | vauthors = Johnson DA, Hricik JG | title = The pharmacology of alpha-adrenergic decongestants | journal = Pharmacotherapy | volume = 13 | issue = 6 Pt 2 | pages = 110S–115S; discussion 143S–146S | date = 1993 | pmid = 7507588 | doi = 10.1002/j.1875-9114.1993.tb02779.x| url = }}</ref><ref name="Broadley2010" /> It is also not metabolized by [[catechol O-methyltransferase|catechol ''O''-methyltransferase]] (COMT).<ref name="ODonnell1995" /> Pseudoephedrine is [[demethylation|demethylated]] into the [[metabolite]] [[cathine|norpseudoephedrine]] to a small extent.<ref name="GłowackaWiela-Hojeńska2021" /><ref name="ChuaBenrimojTriggs1989" /> Similarly to pseudoephedrine, this metabolite is [[active metabolite|active]] and shows [[amphetamine]]-like effects.<ref name="ChuaBenrimojTriggs1989" /> Approximately 1 to 6% of pseudoephedrine is metabolized in the [[liver]] via ''N''-demethylation to form norpseudoephedrine.<ref name="GłowackaWiela-Hojeńska2021" />

====Elimination====
Pseudoephedrine is [[excretion|excreted]] primarily via the [[kidney]]s in [[urine]].<ref name="GłowackaWiela-Hojeńska2021" /><ref name="ChuaBenrimojTriggs1989" /> Its urinary excretion is highly influenced by urinary [[pH]] and is increased when the urine is [[acidic]] and is decreased when it is [[alkaline]].<ref name="GłowackaWiela-Hojeńska2021" /><ref name="ChuaBenrimojTriggs1989" /><ref name="HughesEmpeyLand1983" />

The [[elimination half-life]] of pseudoephedrine on average is 5.4{{nbsp}}hours<ref name="Eccles2007" /> and ranges from 3 to 16{{nbsp}}hours depending on urinary pH.<ref name="GłowackaWiela-Hojeńska2021" /><ref name="ChuaBenrimojTriggs1989" /> At a pH of 5.6 to 6.0, the [[elimination half-life]] of pseudoephedrine was 5.2 to 8.0{{nbsp}}hours.<ref name="ChuaBenrimojTriggs1989" /> In one study, a more acidic pH of 5.0 resulted in a half-life of 3.0 to 6.4{{nbsp}}hours, whereas a more alkaline pH of 8.0 resulted in a half-life of 9.2 to 16.0{{nbsp}}hours.<ref name="ChuaBenrimojTriggs1989" /> Substances that influence urinary acidity and are known to affect the excretion of amphetamine derivatives include [[acidifier|urinary acidifying agents]] like [[ascorbic acid]] and [[ammonium chloride]] as well as [[alkalinizing agent|urinary alkalinizing agents]] like [[acetazolamide]].<ref name="PatrickMarkowitz1997"/>

A majority of an [[oral administration|oral]] dose of pseudoephedrine is excreted unchanged in urine within 24{{nbsp}}hours of administration.<ref name="ChuaBenrimojTriggs1989" /> This has been found to range from 43 to 96%.<ref name="GłowackaWiela-Hojeńska2021" /><ref name="ChuaBenrimojTriggs1989" /><ref name="Eccles2007" /> The amount excreted unchanged is dependent on urinary pH similarly to the drug's half-life, as a longer half-life and duration in the body allows more time for the drug to be metabolized.<ref name="ChuaBenrimojTriggs1989" />

The [[duration of action]] of pseudoephedrine, which is dependent on its [[elimination (pharmacology)|elimination]], is 4 to 12{{nbsp}}hours.<ref name="GłowackaWiela-Hojeńska2021" /><ref name="Aaron1990" />

Pseudoephedrine has been reported to accumulate in people with [[renal impairment]].<ref name="Sequeira1998">{{cite book | vauthors = Sequeira RP N| title=Side Effects of Drugs Annual | chapter=Central nervous system stimulants and drugs that suppress appetite | publisher=Elsevier | volume=21 | date=1998 | isbn=978-0-444-82818-7 | doi=10.1016/s0378-6080(98)80005-6 | pages=1–8}}</ref><ref name="SicaComstock1989">{{cite journal | vauthors = Sica DA, Comstock TJ | title = Pseudoephedrine accumulation in renal failure | journal = Am J Med Sci | volume = 298 | issue = 4 | pages = 261–263 | date = October 1989 | pmid = 2801760 | doi = 10.1097/00000441-198910000-00010 | url = }}</ref><ref name="LyonTurney1996">{{cite journal | vauthors = Lyon CC, Turney JH | title = Pseudoephedrine toxicity in renal failure | journal = Br J Clin Pract | volume = 50 | issue = 7 | pages = 396–397 | date = 1996 | pmid = 9015914 | doi = 10.1111/j.1742-1241.1996.tb09584.x| url = }}</ref>