Morphine Inhalation by Cancer Patients: A Comparison of Different Nebulization Techniques Using Pharmacokinetic, Spirometric, and Gasometric Parameters

Krajnik, Małgorzata; Podolec, Zygmunt; Siekierka, Monika; Sykutera, Marzena; Pufal, Ewa; Sobanski, Piotr; Makarewicz, Roman; Neef, Cees; Punt, Nieko; Zylicz, Zbigniew

doi:10.1016/j.jpainsymman.2009.03.008

« Previous Next »Journal of Pain and Symptom Management
Volume 38, Issue 5 , Pages 747-757, November 2009

Morphine Inhalation by Cancer Patients: A Comparison of Different Nebulization Techniques Using Pharmacokinetic, Spirometric, and Gasometric Parameters

Małgorzata Krajnik, MD
- Department of Palliative Care, Collegium Medicum, Nicolas Copernicus University, Bydgoszcz, Poland
- Address correspondence to: Małgorzata Krajnik, MD, Department of Palliative Care, Collegium Medicum, Nicolas Copernicus University, Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.
Zygmunt Podolec, MD
- Department of Aerosology and Aerosol Bioengineering, Research and Development Centre of MEDiNET, Krakow, Poland
Monika Siekierka, MSci
- Department of Physiology, Collegium Medicum, Nicolas Copernicus University, Bydgoszcz, Poland
Marzena Sykutera, MSci
- Department of Forensic Medicine, Collegium Medicum, Nicolas Copernicus University, Bydgoszcz, Poland
Ewa Pufal, MD
- Department of Forensic Medicine, Collegium Medicum, Nicolas Copernicus University, Bydgoszcz, Poland
Piotr Sobanski, MD
- Cardiology Department, II University Hospital, Bydgoszcz, Poland
Roman Makarewicz, MD, PhD
- Department of Oncology, Collegium Medicum, Nicolas Copernicus University, Bydgoszcz, Poland
Cees Neef, PharmD, PhD
- Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, The Netherlands
Nieko Punt, MSci
- Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, The Netherlands
Zbigniew Zylicz, MD, PhD
- Dove House Hospice, Hull, United Kingdom

Accepted 1 April 2009. published online 25 September 2009.

Abstract

Despite numerous case reports suggesting the value of morphine (M) nebulization in the treatment of breathlessness, only a few clinical trials have been able to support this. The reason for this could lie in the lack of understanding of the localization of opioid receptors in the airways and the biopharmaceutics and pharmacokinetics of nebulized morphine. In the present study, we compared two different methods of pneumodosimetric nebulization: the Bronchial Control Treatment System-Sidestream (BCTS-S) and the Bronchial Control Treatment System-Micro Cirrus (BCTS-MC). The first method delivers relatively large aerosol particles (2–5μm) preferentially to the bronchial tree and trachea. In the BCTS-MC method, small aerosol particles (0.5–2μm) mostly reach the alveoli. Ten patients with cancer were randomly assigned to either the BCTS-S or BCTS-MC inhalation of 5 mg morphine HCl. Patients using the BCTS-S method inhaled a morphine dose in 6.6±2 minutes, whereas with the BCTS-MC method, the inhalation time was 28.8±8 minutes. The areas under the curve of morphine and glucuronides were several times higher after BCTS-S than after BCTS-MC. The proportion of morphine-3-glucuronide to morphine-6-glucuronide (M6) was, on average, close to one for both methods. From the same amount of morphine in the BCTS-S method, five times more M6 was produced. In both methods, the time to maximum concentration for morphine metabolites was 20–40 minutes, much shorter than expected from oral, intranasal, or intravenous administration. The study shows that the method of inhalation may have a profound effect on the pharmacokinetics of morphine. It is possible that the lungs metabolize morphine to glucuronides themselves and in different proportions from those seen after systemic administration. The BCTS-S method was found to be potentially superior to the BCTS-MC method in local action in the lungs.