TY - JOUR
T1 - Topical morphine for oral mucositis in children
T2 - dose finding and absorption
AU - Nielsen, Bettina Nygaard
AU - Aagaard, Gitte
AU - Henneberg, Steen W
AU - Schmigelow, Kjeld
AU - Hansen, Steen Honore'
AU - Rømsing, Janne
PY - 2012/7
Y1 - 2012/7
N2 - Context: Systemic opioids for painful chemotherapy-induced oral mucositis in children often result in unsatisfactory pain relief and a high frequency of side effects. Opioids applied topically can produce analgesia by binding to opioid receptors on peripheral terminals of sensory neurons. These receptors are upregulated during inflammation, for example, in oral mucositis. Objectives: The aims of this study were to investigate the dose-response relationship (n = 7) and the potential absorption of topical morphine (n = 5) across oral mucosa in children with oral mucositis. Methods: The dose-response study was conducted according to a sequential study design (Dixon's Up-and-Down method) for topical morphine doses of 0.025-0.400 mg/kg, with the decrease in oral pain score as the primary outcome. To assess potential absorption across oral mucosa after a single dose of topical morphine of 0.050 mg/kg, blood samples were drawn and the plasma concentrations of morphine and metabolites were determined by high-pressure liquid chromatography. Results: A decrease in oral pain score of ≥36% was achieved in six of seven patients in the dose-response part of the study. Plasma concentrations of morphine and metabolites were well below effective analgesic levels. Conclusion: No obvious dose-response effect was found for topical morphine doses of 0.025-0.400 mg/kg, and topically applied morphine was not absorbed in clinically relevant doses. However, this study was limited by the small number of patients and the allowance of a systemic opioid as rescue medication. Thus, randomized controlled studies are needed to further investigate the analgesic properties of topical morphine.
AB - Context: Systemic opioids for painful chemotherapy-induced oral mucositis in children often result in unsatisfactory pain relief and a high frequency of side effects. Opioids applied topically can produce analgesia by binding to opioid receptors on peripheral terminals of sensory neurons. These receptors are upregulated during inflammation, for example, in oral mucositis. Objectives: The aims of this study were to investigate the dose-response relationship (n = 7) and the potential absorption of topical morphine (n = 5) across oral mucosa in children with oral mucositis. Methods: The dose-response study was conducted according to a sequential study design (Dixon's Up-and-Down method) for topical morphine doses of 0.025-0.400 mg/kg, with the decrease in oral pain score as the primary outcome. To assess potential absorption across oral mucosa after a single dose of topical morphine of 0.050 mg/kg, blood samples were drawn and the plasma concentrations of morphine and metabolites were determined by high-pressure liquid chromatography. Results: A decrease in oral pain score of ≥36% was achieved in six of seven patients in the dose-response part of the study. Plasma concentrations of morphine and metabolites were well below effective analgesic levels. Conclusion: No obvious dose-response effect was found for topical morphine doses of 0.025-0.400 mg/kg, and topically applied morphine was not absorbed in clinically relevant doses. However, this study was limited by the small number of patients and the allowance of a systemic opioid as rescue medication. Thus, randomized controlled studies are needed to further investigate the analgesic properties of topical morphine.
U2 - 10.1016/j.jpainsymman.2011.06.029
DO - 10.1016/j.jpainsymman.2011.06.029
M3 - Journal article
SN - 0885-3924
VL - 44
SP - 117
EP - 123
JO - Journal of Pain and Symptom Management
JF - Journal of Pain and Symptom Management
IS - 1
ER -