Ventilatory responses of healthy subjects to intravenous combinations of morphine and oxycodone under imposed hypercapnic and hypoxaemic conditions.

Abstract:

AIMS:Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. METHODS:A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1:2, 1:1, 2:1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography-MS/MS. RESULTS:'Placebo' treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PetCO(2) = 55 mmHg (V(E55)) decreased to 74% of the subjects' before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. CONCLUSIONS:Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management.

journal_name

Br J Clin Pharmacol

authors

Ladd LA,Kam PC,Williams DB,Wright AW,Smith MT,Mather LE

doi

10.1111/j.1365-2125.2005.02368.x

keywords:

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

524-35

issue

5

eissn

0306-5251

issn

1365-2125

pii

BCP2368

journal_volume

59

pub_type

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    pub_type: 临床试验,杂志文章,多中心研究

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