Excretion fentanyl

Pharmacokinetic properties Fentanyl (Scholz et al., 1996) is a highly lipophilic compound and about 80% binds to plasma proteins. After parenteral administration it has a rapid onset and a short duration of action. The compound is rapidly transported into the CNS and lipid tissues. The short duration of action is due to redistribution rather than metabolic inactivation or excretion. It is released from tissue depots with a half-life of about 4 h and the terminal half-life is up to 7 h. The main metabolites, excreted in urine are 4-N-(N-propionylanilino)-piperidine and the N-hydroxypropionyl derivative. 

Disposition in the Body. Rapidly metabolised in the liver. Two metabolites, norfentanyl and despropionylfentanyl, have been detected in plasma at concentrations similar to those of fentanyl. About 70% of a dose is excreted in the urine in 72 hours, mostly as metabolites, with about 10 to 20% of a dose being excreted as unchanged drug in 48 hours. About 9% of a dose is eliminated in the faeces. 

Fentanyl is also hepatically metabolized and renally excreted. However, the congener remifentanil is metabolically distinct when compared to other members in its chemical or pharmacological class. Remifentanil is metabolized by plasma esterases to remifentanil acid, which is approximately 3000-fold less potent than the parent opioid (67). 

The choice of a perioperative opioid is based primarily on duration of action, given that at appropriate doses, all produce similar aualgesia aud side effects. Remifentanil has an ultra-short duration of action ( 10 minutes) and accumulates minimally with repeated doses or infusion it is particularly well suited for procedmes that are briefly painful, but for which little analgesia is required postoperatively. Single doses of fentanyl, alfentanil, and sufentanil all have similar intermediate durations of action (30, 20, and 15 minutes, respectively), but recovery after prolonged adminisbation varies considerably. FentanyTs duration of action lengthens most with infusion, sufentanil s much less so, and alfentanil s the least. Except for remifentanil, all of the afore-mentioned opioids are metabolized in the liver followed by renal and biliary excretion of the metabolites. Remifentanil... 

It exhibits a profile of pharmacological action very much identical to morphine, and differs exceptionally on two accounts, namely flrst-it does not cause emesis secondly, it does not release histamine. Its safety measure in frequency cases has not yet been fully understood. It is observed to cross the placental barrier therefore, its usage during labour may ultimately give rise to respiratory depression in the newly bom infant. However, Fentanyl s transient action after the parenteral administration is caused solely on account of redistribution, rather than to "metabolism" or "excretion". Hence, longer usage of this drug may cause in accumulation and toxicities. 

Fentanyl s short duration of action after parenteral dose is caused by redistribution rather than by metabolism or excretion. Repeated doses of fentanyl can result in accumulation and toxicities. Elderly patients usually are more sensitive to fentanyl and require lower doses. 

Fentanyl is excreted primarily by the kidneys, 90% as metabolites, 10% as unchanged drug. 

D uration of action of epidural sufentanil is between that of fentanyl and morphine, usually between 2 and 4 hours. Once systemically absorbed it is metabohzed by the liver and excreted by the kidney. 

As with aU patient-controUed systems and devices, the patient must be capable of understanding how and when to use the system. Consequently it is not appropriate in patients with altered levels of consciousness or unpaired cognition. The system has not been adequately studied in pediatric patients. Fentanyl is highly lipid-soluble. It crosses the placenta to the fetus in pregnancy and is excreted in breast mftk. 

There is also concern over occupational exposure to fentanyl. Fentanyl contamination and urinary excretion has been noted in pharmaceutical industry employees although no sings of toxicity were reported." Exposure and toxicity may occur in health care workers. "" There is also concern over exposure to fentanyl in operating rooms, and the phenomenon of second-hand exposures to fentanyl, with ensuing addiction in health care workers, and especially physicians, anaesthetists and surgeons where there is a recognised problem of drug abuse." " ... 

---