Pharmacokinetics of Intranasal Hydromorphone
Background and Objective: Narcotic analgesics such as hydromorphone undergo an extensive first-pass effect resulting in a low systemic bioavailability following oral administration. Alternative dosing routes, such as rectal and intranasal (IN) routes, have been suggested as options for oral or intravenous administration. Rhinitis and pharmacological agents used for treatment are considered factors that could alter the rate and extent of absorption of drugs administered by the nasal route. The purpose of this study was to evaluate the pharmacokinetics of intranasal hydromorphone hydrochloride (HCl) in patients with vasomotor rhinitis.
Methods: Ten patients completed the randomised, three-way crossover study. During the three treatment periods, a single dose of hydromorphone HCl 2.0mg was administered via intravenous infusion (treatment A) and the intranasal route without (treatment B) or with (treatment C) vasoconstrictor pretreatment for rhinitis. Blood samples were collected serially from 0 to 16 hours. Noncompartmental methods were used to determine pharmacokinetic parameters.
Results: Maximum plasma concentrations were 3.69 and 3.38 μg/L for treatments B and C, respectively. Mean (% coefficient of variation) bioavailability of intranasal hydromorphone was 54.4% (34.8) and 59.8% (22.1) with and without pretreatment, respectively. Pretreatment of rhinitis did not significantly affect the rate or extent of absorption of hydromorphone in this study. There was not a significant difference in bioavailability between treated and untreated rhinitis.
Conclusions: This study found intranasal administration of hydromorphone in patients experiencing vasomotor rhinitis had acceptable bioavailability and a pharmacokinetic profile comparable to previous studies. These data support further investigation of this single-dose delivery system for clinical use.
Hydromorphone, a μ-selective opioid agonist, is a semisynthetic derivative of morphine used for the management of postoperative pain and moderate-to-severe chronic pain associated with terminal illnesses, such as cancer. On a milligram basis, hydromorphone is 5–8.5 times as potent as morphine when given by the oral route, and 5–7.5 times as potent as morphine when given intravenously. Narcotic analgesics such as hydromorphone and morphine have been suggested to undergo an extensive first-pass effect resulting in a low systemic bioavailability following oral administration. Similar to morphine, hydromorphone has been reported to have wide interindividual variation of oral bioavailability ranging from 10% to 65%.
Alternative dosing routes, such as rectal and intranasal (IN), have been suggested as options for oral or intravenous administration of opioids. Rectal administration of hydromorphone has been evaluated in healthy adults and found to have low bioavailability (33%) with wide interindividual variation (10–65%). Factors potentially influencing rectal bioavailability include poor absorption from the rectal mucosa because of high ionisation, small rectal surface area, slow release from the suppository, reduced contact with the rectal epithelial tissue, and first-pass elimination.
The IN route potentially improves systemic bioavailability of drugs since it bypasses gastrointestinal degradation and the hepatic first-pass effect. Potential advantages of IN administration include ease of administration, rapid onset and patient control. There are also potential benefits in safety with the avoidance of needles associated with intravenous (IV) or intramuscular (IM) administration. An alternative dosing route may also be valuable in patients experiencing nausea and vomiting or in the paediatric setting. Other narcotics, such as alfentanil, butorphanol, buprenorphine, fentanyl, oxycodone and sufentanil, have been evaluated in humans following intranasal administration with favourable results.
Rhinitis, inflammation of the nasal mucosa, is a common condition in which the permeability of the nasal mucosa increases, nasal blood flow increases, and secretions permeate out of the nasal glands. Chronic rhinitis is classified by aetiology as allergic or nonallergic. Allergic rhinitis is the most prevalent type of chronic rhinitis, but 30–50% of patients diagnosed with rhinitis may have nonallergic causes. Vasomotor rhinitis is a subtype of nonallergic rhinitis and described as chronic, noninfectious rhinitis usually without nasal eosinophilia. Vasomotor rhinitis manifests as nasal symptoms (rhinorrhoea, nasal congestion, sneezing and postnasal drip) that occur in response to environmental conditions such as cold air, high humidity, strong odours and inhaled irritants. Rhinitis, regardless of aetiology, is considered a factor that could alter the rate and extent of absorption of drugs administered by the nasal route. Moreover, it is also common for patients with rhinitis to use nasal vasoconstrictors or oral decongestants as treatment. Treatment with these agents could theoretically alter the extent and rate of nasal absorption of other medications.
The objectives of this study were to assess the absolute bioavailability and single-dose tolerance of intranasal hydromorphone hydrochloride (HCl), and the effect of an oral decongestant (pseudoephedrine) or nasal vasoconstrictor (oxymetazoline) on the rate or extent of absorption of IN hydromorphone in patients experiencing vasomotor rhinitis.
Background and Objective: Narcotic analgesics such as hydromorphone undergo an extensive first-pass effect resulting in a low systemic bioavailability following oral administration. Alternative dosing routes, such as rectal and intranasal (IN) routes, have been suggested as options for oral or intravenous administration. Rhinitis and pharmacological agents used for treatment are considered factors that could alter the rate and extent of absorption of drugs administered by the nasal route. The purpose of this study was to evaluate the pharmacokinetics of intranasal hydromorphone hydrochloride (HCl) in patients with vasomotor rhinitis.
Methods: Ten patients completed the randomised, three-way crossover study. During the three treatment periods, a single dose of hydromorphone HCl 2.0mg was administered via intravenous infusion (treatment A) and the intranasal route without (treatment B) or with (treatment C) vasoconstrictor pretreatment for rhinitis. Blood samples were collected serially from 0 to 16 hours. Noncompartmental methods were used to determine pharmacokinetic parameters.
Results: Maximum plasma concentrations were 3.69 and 3.38 μg/L for treatments B and C, respectively. Mean (% coefficient of variation) bioavailability of intranasal hydromorphone was 54.4% (34.8) and 59.8% (22.1) with and without pretreatment, respectively. Pretreatment of rhinitis did not significantly affect the rate or extent of absorption of hydromorphone in this study. There was not a significant difference in bioavailability between treated and untreated rhinitis.
Conclusions: This study found intranasal administration of hydromorphone in patients experiencing vasomotor rhinitis had acceptable bioavailability and a pharmacokinetic profile comparable to previous studies. These data support further investigation of this single-dose delivery system for clinical use.
Hydromorphone, a μ-selective opioid agonist, is a semisynthetic derivative of morphine used for the management of postoperative pain and moderate-to-severe chronic pain associated with terminal illnesses, such as cancer. On a milligram basis, hydromorphone is 5–8.5 times as potent as morphine when given by the oral route, and 5–7.5 times as potent as morphine when given intravenously. Narcotic analgesics such as hydromorphone and morphine have been suggested to undergo an extensive first-pass effect resulting in a low systemic bioavailability following oral administration. Similar to morphine, hydromorphone has been reported to have wide interindividual variation of oral bioavailability ranging from 10% to 65%.
Alternative dosing routes, such as rectal and intranasal (IN), have been suggested as options for oral or intravenous administration of opioids. Rectal administration of hydromorphone has been evaluated in healthy adults and found to have low bioavailability (33%) with wide interindividual variation (10–65%). Factors potentially influencing rectal bioavailability include poor absorption from the rectal mucosa because of high ionisation, small rectal surface area, slow release from the suppository, reduced contact with the rectal epithelial tissue, and first-pass elimination.
The IN route potentially improves systemic bioavailability of drugs since it bypasses gastrointestinal degradation and the hepatic first-pass effect. Potential advantages of IN administration include ease of administration, rapid onset and patient control. There are also potential benefits in safety with the avoidance of needles associated with intravenous (IV) or intramuscular (IM) administration. An alternative dosing route may also be valuable in patients experiencing nausea and vomiting or in the paediatric setting. Other narcotics, such as alfentanil, butorphanol, buprenorphine, fentanyl, oxycodone and sufentanil, have been evaluated in humans following intranasal administration with favourable results.
Rhinitis, inflammation of the nasal mucosa, is a common condition in which the permeability of the nasal mucosa increases, nasal blood flow increases, and secretions permeate out of the nasal glands. Chronic rhinitis is classified by aetiology as allergic or nonallergic. Allergic rhinitis is the most prevalent type of chronic rhinitis, but 30–50% of patients diagnosed with rhinitis may have nonallergic causes. Vasomotor rhinitis is a subtype of nonallergic rhinitis and described as chronic, noninfectious rhinitis usually without nasal eosinophilia. Vasomotor rhinitis manifests as nasal symptoms (rhinorrhoea, nasal congestion, sneezing and postnasal drip) that occur in response to environmental conditions such as cold air, high humidity, strong odours and inhaled irritants. Rhinitis, regardless of aetiology, is considered a factor that could alter the rate and extent of absorption of drugs administered by the nasal route. Moreover, it is also common for patients with rhinitis to use nasal vasoconstrictors or oral decongestants as treatment. Treatment with these agents could theoretically alter the extent and rate of nasal absorption of other medications.
The objectives of this study were to assess the absolute bioavailability and single-dose tolerance of intranasal hydromorphone hydrochloride (HCl), and the effect of an oral decongestant (pseudoephedrine) or nasal vasoconstrictor (oxymetazoline) on the rate or extent of absorption of IN hydromorphone in patients experiencing vasomotor rhinitis.