Clinical Pharmacokinetics of Alfentanil, Fentanyl and Sufentanil

Abstract

Alfentanil, fentanyl and sufentanil are synthetic opioid analgesics acting at specific opioid receptors. These opioids are widely used as analgesics to supplement general anaesthesia for various surgical procedures or as primary anaesthetic agents in very high doses during cardiac surgery. Fentanyl and sufentanil especially are administered via infusion for long term analgesia and sedation in intensive care patients. Opioid analgesics are mainly administered using the intravenous route. However, other techniques of administration, including epidural, intrathecal, transdermal and intranasal applications, have been demonstrated. Important pharmacokinetic differences between alfentanil, fentanyl and sufentanil have been shown in many reports. Alfentanil has the most rapid analgesic onset and time to peak effect as well as the shortest distribution and elimination half-lives. The volume of distribution and total body clearance of this agent are smaller when compared with those of fentanyl and sufentanil. The pharmacokinetics of the opioid analgesics can be affected by several factors including patient age, plasma protein content, acid-base status and cardiopulmonary bypass, but not significantly by renal insufficiency or compensated hepatic dysfunction. In addition, pharmacokinetic properties can be influenced by changes in hepatic blood flow and administration of drug combinations which compete for the same plasma protein carrier or metabolising pathway. Although comparing specific pharmacokinetic parameters such as half-lives is deeply entrenched in the literature and clinical practice, simply comparing half-lives is not a rational way to select an opioid for specific requirements. Using pharmacokinetic-pharmacodynamic models, computer simulations based on changes in the effect site opioid concentration or context-sensitive half-times seem to be extremely useful for selecting an opioid on a more rational basis.

Prolonged recovery and respiratory depression after fentanyl infusion in a sheep undergoing mitral valve reconstruction

“…Cardiopulmonary bypass significantly changes the pharmacokinetics of opioids in human patients (Scholz et al 1996). This is due to altered distribution volumes (secondary to priming of the ECC), acid-base, organ blood flow, plasma protein concentration and body temperature alterations (Gedney & Ghosh 1995).…”

Effects of Intravenous Fentanyl Administration on End-Tidal Sevoflurane Concentrations in Thoroughbred Racehorses undergoing Orthopedic Surgery

“…However, the use of NSAIDs alone can be insufficient to adequately alleviate serve pain in conditions such as orthopedic diseases. On the other hand, fentanyl is a synthetic -opioid receptor agonist of the 4-anilinopiperidine series that is commonly used as an analgesic for moderate to serve pain in a number of species [17]. In humans and small animals, balanced anesthesia with fentanyl provides perioperative analgesia and improves hemodynamics by minimizing the necessary inhalation concentration of anesthetic agents for general anesthesia [11,12,23].…”

Pharmacokinetics and Pharmacodynamics of Alfentanil in P-Glycoprotein-Competent and P-Glycoprotein-Deficient Mice: P-Glycoprotein Efflux Alters Alfentanil Brain Disposition and Antinociception

“…Alfentanil is a synthetic opioid used for the induction of surgical anesthesia and the management of postsurgical pain. The alfentanil dose needs to be individualized based on numerous factors, including pathological condition, use of other medicines, and the type and duration of the surgical procedure (Scholz et al, 1996). Because alfentanil is a CYP3A4 substrate, CYP3A4 activity is another important determinant of the required alfentanil dose (Kharasch and Thummel, 1993).…”