Pharmacokinetics of Dextromoramide in Surgical Patients

Abstract

The pharmacokinetics of the narcotic analgesic dextromoramide was investigated by means of a specific GC-MS method in 9 patients who were given a single oral dose of the drug (7.5 mg) together with an anticholinergic before undergoing minor orthopedic surgery. Dextromoramide was rapidly absorbed from the gastrointestinal tract, with peak plasma levels between 68 and 177 micrograms/L usually achieved within 0.5-4.0 h after dosing. In 5 patients, the decline of plasma concentrations after the peak followed a biphasic pattern, with half-lives of 0.4-1.6 h for the first phase and 6.3-21.8 h for the terminal phase. In the remaining patients, no clear-cut biphasic pattern was seen and half-lives calculated over the period between 4 h and 10 h after administration ranged from 1.5 to 4.7 h. Apparent clearance and volume of distribution values ranged from 0.06 to 0.36 1.h-1.kg-1 and from 0.6 to 2.4 l.kg-1, respectively. Less than 0.06% of the dose was excreted unchanged in urine within 8 h of administration. The concentration of the drug in a CSF sample collected 1 h after dosing was below the limit of detection (2 micrograms/L) in all subjects.

Beyond the end of the line: Case reports of conversion from dextromoramide to other opiates within addiction maintenance treatment

“…Additionally, it is not simply a matter of establishing the equipotent dose for a single dose, since the pharmacokinetics of the drug may change with repeated administration, alongside the need to consider accumulation of drug with repeated administration (Edwards & Lader, 1990;Goodman & Gilman, 1980). Furthermore, with dextromoramide in particular, the duration of action of a given dose is likely to be variable both between patients and within an individual patient over time, since dextromoramide has been reported to have a two-phase elimination (Dollery, 1999;Pagani et al, 1989) with, on repeated administration, a terminal half-life of 6.3-21.8 hours (in contrast to the initial half-life of 0.4-1.6 hours).…”

Treatment of pain in patients with renal insufficiency: The World Health Organization three-step ladder adapted

“…Less than 1% of a dose is excreted unchanged in the urine 8 hours after administration. 91 Thus, dosing adjustment is unlikely to be necessary in patients with renal insufficiency. Volume of distribution appears to be low, and dextromoramide is thought to be such highly protein bound that it is certainly not dialyzable to a clinically significant extent.…”

Chemoenzymatic Synthesis of Optically Active Ethereal Analog of iso-Moramide—A Novel Potentially Powerful Analgesic †

“…Dextromoramide was introduced in 1956 by Dr. Paul Janssen [ 4 , 5 , 6 , 7 ], and shortly after discovering that it is a μ -agonist analgesic two to four times more powerful than morphine [ 8 ], it became a popular drug in pharmacologic pain therapy. Unfortunately, although dextromoramide is an ultra-efficient pharmaceutical against violent (intense) pain that standard doses of other opiates can hardly alleviate, it suffers from two major limitations: it is highly addictive and induces respiratory depression [ 9 ].…”