Disease relevance of ALFENTANIL

• 58 temporal lobe epilepsy (TLE) patients were studied with alfentanil activation during electrocorticography, at the Epilepsy Surgery Unit (ING, Brazil) [1].
• Dose-dependent alfentanil disposition was mirrored by commensurate changes in clinical effect, although miosis was variable and not detectable in all subjects at the lowest dose [2].
• Significant and marked reductions of hyperalgesia to cold (visual analogue score at threshold value) were seen following both alfentanil (4.5 before, 1.4 after, median value) and ketamine (6.8 before, 0.4 after, median value) [3].
• Of the newer analgesic agents, alfentanil is an ideal agent for infusion, and may be the agent of choice in renal failure [4].
• The difficulties in accurately predicting the response of an individual critically ill patient necessitate careful and continuous dose titration of alfentanil according to the clinical response [5].

Psychiatry related information on ALFENTANIL

• The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect [6].
• We observed noteworthy individual differences in analgesic response with all 3 drugs but these differences were greatest for morphine and least for alfentanil [7].
• Alcohol consumption alters the pharmacodynamics of alfentanil [8].
• Apparent pA2 analysis was used to determine whether the short-duration opioid agonist, alfentanil, acts at mu receptors in the positive reinforcement of operant behavior in the rhesus monkey [9].
• OBJECTIVES: Dose-response relationships of drug reinforcers (remifentanil, alfentanil, morphine, cocaine) as well as a physiological reinforcer, i.e. food (sweetened condensed milk) were investigated in a different operant conditioning paradigm, i.e. a runway procedure [10].

High impact information on ALFENTANIL

• It is reasonable to assume that patients receiving voriconazole require 70% to 90% less alfentanil for the maintenance of analgesia than patients who are not receiving concomitant CYP3A inhibitors [11].
• Terbinafine had no statistically significant effect on the pharmacokinetics of alfentanil [11].
• Concomitant administration of alfentanil and CYP3A inhibitors may lead to clinically important drug interactions [11].
• INTRODUCTION: The clearances of oral and intravenous alfentanil are in vivo probes for assessing first-pass and hepatic cytochrome P450 (CYP) 3A activity [12].
• Single-point sampling for assessment of constitutive, induced, and inhibited cytochrome P450 3A activity with alfentanil or midazolam [12].

Chemical compound and disease context of ALFENTANIL

• Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions [6].
• Cold allodynia and hyperalgesia in neuropathic pain: the effect of N-methyl-D-aspartate (NMDA) receptor antagonist ketamine--a double-blind, cross-over comparison with alfentanil and placebo [3].
• CONCLUSIONS: Alfentanil significantly reduces blood propofol concentrations required for loss of eyelash reflex and loss of consciousness [13].
• To determine whether this effect was caused by changes in nociception, this study prospectively evaluated the influence of an experimental focal brain injury on the analgesic effects of the opioids, fentanyl and alfentanil, in rats [14].
• We studied the effects of continuous infusion of remifentanil, compared with alfentanil, on the respiratory response to hypoxia [15].

Biological context of ALFENTANIL

• Oral alfentanil effect may be a noninvasive surrogate for conventional pharmacokinetics [2].
• CONCLUSION: Oral alfentanil is rapidly absorbed, exhibits linear and dose-independent kinetics, and undergoes substantial first-pass metabolism [2].
• The relationship between alfentanil distribution kinetics and cardiac output [16].
• Alfentanil and midazolam area under the concentration-time curve (AUC) was calculated by noncompartmental analysis [12].
• The relationship between cardiac output and the tissue distribution of alfentanil was investigated in seven healthy volunteers [16].

Anatomical context of ALFENTANIL

• In summary, our study confirms the activating effect of alfentanil, and provides a strong evidence for its selective activating effect on the temporal lobes of TLE patients [1].
• In this study, we employed the PKPCA system to compare efficacy and side-effect intensities of 2 mu-selective opioid analgesics, alfentanil and morphine, in bone marrow transplant (BMT) patients self-administering the drugs to relieve pain from oral mucositis [17].
• Self-administered alfentanil during ESWL of gallbladder stones provided adequate analgesia with minimal side effects and high patient satisfaction [18].
• Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting [19].
• These pharmacokinetic data demonstrate that liposome encapsulation resulted in a slow but prolonged appearance of free alfentanil into a diffusible pool available for uptake into the spinal cord [20].

Associations of ALFENTANIL with other chemical compounds

• Metabolism of cytochrome P4503A substrates in vivo administered by the same route: lack of correlation between alfentanil clearance and erythromycin breath test [21].
• No significant correlation was found between alfentanil metabolism and the erythromycin breath test: alfentanil clearance versus erythromycin breath test, r = 0.45, p = 0.1; partial metabolic clearance to noralfentanil versus erythromycin breath test, r = 0.35, p = 0.23 [21].
• These results suggest that mechanisms other than perivascular hydrogen ion concentration mediate the CBF response to changes in arterial CO2 tension during alfentanil anesthesia [22].
• Trefentanil versus alfentanil pharmacokinetic parameters were as follows: Elimination clearance, 0.444 +/- 0.073 versus 0.184 +/- 0.031 L/min; steady-state distribution volume, 37 +/- 7 versus 23 +/- 3 L; and elimination half-life, 127 +/- 24 versus 114 +/- 19 minutes [23].
• RESULTS: Voriconazole decreased the mean plasma clearance of intravenous alfentanil by 85%, from the control value of 4.4 +/- 2.4 mL . min(-1). kg(-1) to 0.67 +/- 0.27 mL . min(-1). kg(-1) (P < .001), and prolonged its elimination half-life from 1.5 +/- 0.49 hours to 6.6 +/- 1.8 hours (P < .001) [11].

Gene context of ALFENTANIL

• Alfentanil undergoes extensive metabolism by cytochrome P4503A4 (CYP3A4) [24].
• There was a poor correlation between alfentanil metabolism and CYP3A4 content but an excellent correlation when CYP3A5 (i.e., total CYP3A content) was considered (r = 0.81, P < 0.0001) [24].
• Pharmacogenetic determinants of human liver microsomal alfentanil metabolism and the role of cytochrome P450 3A5 [24].
• There was a significant correlation (r = 0.97, P < 0.001) between alfentanil systemic clearance and P450 3A4 activity [25].
• Alfentanil is a selective CYP3A probe but not a P-gp substrate [26].

Analytical, diagnostic and therapeutic context of ALFENTANIL

• Postoperative analgesia with intravenous infusion of alfentanil [27].
• Alfentanil infusion for sedation and analgesia in intensive care [28].
• The ictal SPECT during alfentanil activation did not offer any additional advantage for the localization of the ictal onset [1].
• Dose effects of alfentanil in human analgesia [29].
• RESULTS: Alfentanil induced a high-amplitude low-frequency EEG response [30].

References