Naloxone nasal spray - bioavailability and absorption pattern in a phase 1 study.

Background: Bystander administration with naloxone nasal spray can prevent deaths from opioid overdose. To achieve optimal nasal absorption of naloxone, the spray must be administered at low volume with high concentration of the drug. The study aimed to investigate the bioavailability and absorption pattern for a new naloxone nasal spray.

Pharmacodynamics and arteriovenous difference of intravenous naloxone in healthy volunteers exposed to remifentanil.

Purpose: Pharmacodynamic studies of naloxone require opioid agonism. Steady state condition may be achieved by remifentanil TCI (target controlled infusion). Opioid agonism can be measured by pupillometry.

Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers.

Purpose: This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg.

Methods: Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min.

Pharmacokinetics of a new, nasal formulation of naloxone.

Purpose: Nasal naloxone is wanted for bystander administration in opioid overdose and as a needle-free alternative for emergency medical personnel. Epidemiologic studies have indicated a therapeutic effect of bystander administration of low-concentration/high-volume formulations. The objective for this study was to describe the nasal pharmacokinetics of a new high-concentration/low-volume nasal formulation of naloxone.

Effects of hypothermia on the disposition of morphine, midazolam, fentanyl, and propofol in intensive care unit patients.

Therapeutic hypothermia (TH) may induce pharmacokinetic changes that may affect the level of sedation. We have compared the disposition of morphine, midazolam, fentanyl, and propofol in TH with normothermia in man. Fourteen patients treated with TH following cardiac arrest (33-34°C) were compared with eight matched critically ill patients (36-38°C).

Early pharmacokinetics of nasal fentanyl: is there a significant arterio-venous difference?

Objective: We have investigated the arterio-venous difference in the pharmacokinetics of 50 microg fentanyl during the first hour following nasal administration and documented its tolerability in opioid-naïve middle-aged to elderly patients.

Methods: Twelve male patients (range in age 47-84 years) scheduled for transurethral resection of the prostate gland received a 100-microl dose of 50 microg fentanyl base as a fentanyl citrate formulation in one nostril. Simultaneous arterial and venous blood samples for analyses of fentanyl were drawn at baseline and at 1, 3, 5, 7, 9, 13, 15, 20, 25, 35, 45 and 60 min after drug administration.

Intranasal midazolam: a comparison of two delivery devices in human volunteers.

Bidirectional nasal drug delivery is a new administration principle with improved deposition pattern that may increase nasal drug uptake. Twelve healthy subjects were included in this open, non-randomized 3-way crossover study: midazolam (3.4 mg) intravenously (1 mg mL (-1)), or nasally by bidirectional or traditional spray (2 x100 microL of a 17 mg mL(-1) nasal midazolam formulation).

Transepithelial transport of morphine and mannitol in Caco-2 cells: the influence of chitosans of different molecular weights and degrees of acetylation.

The object of this study was to compare the effect of chitosans of different number-average molecular weights (MWs) and degrees of acetylation (F(A)) on transepithelial transport of morphine in Caco-2 cells. Caco-2 monolayers on polycarbonate (PC) membranes (0.5 cm(2)) were incubated with morphine (10 microM) or mannitol (55 microM) for 180 min.

A validated method for rapid analysis of ethane in breath and its application in kinetic studies in human volunteers.

Oxidative stress may initiate lipid peroxidation that generates ethane. Ethane, at low concentrations, is eliminated by pulmonary exhalation. Previous methods have not allowed frequent sampling, thus ethane kinetics has not been studied in man.

Effects of food on the pharmacokinetics of levodopa in a dual-release formulation.

The objective was to assess the effect of food on the pharmacokinetics of levodopa and 3-O-methyldopa after administration of a new levodopa/benserazide formulation with a dual-release drug delivery profile (Madopar DR). In an open-label, two-way cross-over study, 19 healthy volunteers who had fasted overnight were randomized to receive a single oral dose of levodopa/benserazide (200/50 mg) in the absence or presence of a standardized, high-fat breakfast, administered 30 min before drug administration. The treatment periods (fasting, non-fasting) were preceded by a baseline regimen of levodopa/benserazide (100/25 mg t.

Chronic exposure to carbon monoxide and nicotine: endothelin ET(A) receptor antagonism attenuates carbon monoxide-induced myocardial hypertrophy in rat.

The aims of the present study were to determine the effects of endothelin ET(A) receptor antagonism on carbon monoxide (CO)-induced cardiac hypertrophy and endothelin-1 (ET-1) expression and to compare myocardial effects of chronic nicotine with CO exposure. Female Sprague-Dawley rats (n = 84) were randomized to three groups exposed 20 h/day to CO (200 ppm), nicotine (500 microg/m3), or air for 14 consecutive days. In each exposure group, animals were randomized to ET(A) receptor antagonist LU 135252 in drinking water (0.