Background: Fentanyl, a short-acting constructed opioid, has a pharmacokinetic contour ill-fitted to fast abatement of abrupt anecdotal pain.Objective: To characterize the pharmacokinetic-pharmacodynamic alternation of intranasal and intravenous fentanyl in opioid-naïve patients ability third molar extraction.Methods: A double-blind, double-dummy, crossover architecture abstraction was conducted, with patients randomized to accept 1 of 4 fentanyl doses (75, 100, 150, or 200 µg) by both the intravenous and intranasal routes. Venous fentanyl concentrations were bent for up to 180 account and affliction array were recorded up to 240 account postdose. Continuance of aftereffect and time to accomplishment medication were additionally recorded.Results: The pharmacokinetics of intravenous fentanyl reflected a 2-compartment archetypal with a approval of about 1.5 L/min. There was abstinent (< 50%) between-subject airheadedness (BSV; %CV [coefficient of variation]) in the systemic kinetics of fentanyl. Bioavailability of intranasal fentanyl was 89%, afterward first-order absorption, with a lag of about 5 account and a half-life of about 6.5 minutes. Interpatient assimilation airheadedness was about 30% BSV for all assimilation parameters. Intranasal against intravenous administering led to a delayed beggarly fentanyl time to best assimilation (13 vs 6 min) and lower best assimilation (1.2 vs 2.0 ng/mL). Analgesic aftereffect lagged abaft the venous fentanyl concentration, with a half-life of about 2.5 account as declared by a apportioned arced best biologic aftereffect activating model. The concentration-analgesia accord was steep, with a 50% able assimilation of 0.46 ng/mL (Hill accessory 3.5). Intranasal admission and account of analgesia were hardly delayed, principally due to the adjournment and lag in systemic absorption, with hardly lower aiguille analgesic effect, compared with intravenous fentanyl. Continuance of aftereffect was anon accompanying to intranasal fentanyl dose, with affliction array abiding to predose ethics at about 120 account (75 µg) to about 240 account (200 µg) afterwards a distinct dose.Conclusions: Intranasal fentanyl showed active and activating backdrop that are adorable for the administering of acute, anecdotal (breakthrough) pain.
Intranasal opioid administering after-effects in a accelerated admission of activity and a almost abbreviate continuance of effect.[1] Fentanyl may be an ideal biologic for intranasal administration, actuality both lipophilic and almighty (50- to 100-fold added so than morphine) and rapidly captivated through the nasal mucosa. Furthermore, fentanyl shows little bounded affliction afterwards nasal administration.[2] Such a approach of analgesic administering ability be ideal for patients with salivary gland dysfunction (dry aperture syndrome), nausea, vomiting, or broken gastrointestinal absorption.
Two studies on the pharmacokinetics of intranasally administered fentanyl accept apparent it to be rapidly captivated through the nasal mucosa, with time to best assimilation (tmax) 5-40 and 4-11 minutes, application a 50-µg dose.[3,4] Bioavailability was 71%, but with aerial interindividual variation.[3] Bioavailability has been appropriate to be pH dependent, with 55% and 71% abstinent at pH 6.0 and pH 8.0, respectively, although these allegation were not decidedly different.[4] Recently, we advised the pharmacokinetics of fentanyl application doses of 75, 100, 150, and 200 µg, which were accustomed both intravenously and intranasally.[5] Linear relationships amid dosage and the area-under-the-concentration-time ambit to 3 hours (AUC0-3) were begin for both routes of administration. For the 4 doses pooled, although AUC0-3-nasal was college than AUC0-3-intravenous, the differences were not statistically significant. Aiguille assimilation afterwards intranasal fentanyl was 71% against intravenous (p = 0.016). The tmax was begin to be decidedly different, with the beggarly ethics 12.8 account afterwards intranasal and 6.0 account afterwards intravenous administering (p < 0.0001).[5]
Intranasal administering of fentanyl has apparent a fast admission of analgesic activity back acclimated for premedication in children, postoperative pain, astute affliction in emergency departments, procedural anguish affliction pain, and cancer-related advance pain.[2,6,7,8,9,10,11,12,13,14,15,16]
The pharmacokinetic-pharmacodynamic relationships of opioids accept been again assessed, application electroencephalogram (EEG)-derived parameters, adherent size, and beginning and analytic affliction as aftereffect measures. The analgesic aftereffect (pharmacodynamic) usually parallels claret concentrations but with a banausic shift. This about-face is accounted for by the addition of a academic aftereffect compartment, which is affiliated to the claret alcove by a first-order alteration activity with an abolishment amount connected (ke0). This represents the adjournment in the admission of the biologic to the armpit of action, apparently the axial afraid system. In all of 4 appear studies that advised EEG-derived parameters, the half-life of equilibration for the aftereffect alcove [t1/2 (ke0)] was appear to be about 5 minutes.[17,18,19,20] However, to date, we are acquainted of no studies on the pharmacokinetic-pharmacodynamic relationships of fentanyl application analytic affliction as the activating acknowledgment to accept been agitated out. The aim of this abstraction was to characterize the alternation amid claret concentration-time profiles and the time advance of affliction acuteness abridgement afterward intravenous and intranasal administering of fentanyl in patients ability third molar extraction.
How To Find Molar Concentration – How To Find Molar Concentration
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