Oral-Parenteral Conversion Factor for Morphine in Palliative Cancer Care: A Prospective Randomized Crossover Pilot Study

Abstract

Objective. This pilot study clinically tests whether a conversion factor of 2 to 1 is appropriate when changing from oral to parenteral morphine administration in the treatment of cancer-related nociceptive pain and calculates the size of an adequately powered future study. Methods. Eleven outpatients with incurable cancer and well-controlled nociceptive pain were randomly assigned to either intravenous or subcutaneous morphine using half the previous oral 24-hour dose. Each group crossed over after the first three-day period. Serum concentrations of morphine and its metabolites were monitored as well as intensity of pain. Results. Oral to subcutaneous and oral to intravenous quotas of morphine concentrations were approximately 0.9. Subcutaneous to intravenous morphine quotas were 1. Conclusions. The conversion factor of 2 to 1 seems to be a reasonable average but with an obvious need for individual adjustments. Concurrent medications and substantially higher doses of morphine could potentially affect the appropriate conversion factor. An adequately powered study to validate these findings would need at least 121 patients.

A Prospective Population Pharmacokinetic Study on Morphine Metabolism in Cancer Patients

“…Although information available in the literature was limited, i.e. the studies comparing subcutaneous and intravenous administration usually involved a small number of patients and a crossover design was not used in all studies [ 29 – 31 ], we consider that the current literature supports the assumption made. The main consequence if this assumption is not true lies in the interpretation of the estimated pharmacokinetic parameters, i.e.…”

“…Oral bioavailability was estimated under the assumption of complete subcutaneous bioavailability, as indicated in the current literature [29–31]. Thereafter, the model was extended to also describe the pharmacokinetics of the metabolites.…”

“…First, a pharmacokinetic model was developed for morphine following subcutaneous and oral administration, starting out from previously published models [ 27 , 28 ]. Oral bioavailability was estimated under the assumption of complete subcutaneous bioavailability, as indicated in the current literature [ 29 – 31 ]. Thereafter, the model was extended to also describe the pharmacokinetics of the metabolites.…”

Pharmacokinetics of Morphine, Morphine-3-Glucuronide and Morphine-6-Glucuronide in Terminally Ill Adult Patients

“…The data were log-transformed and concentrations of M3G and M6G were adjusted to their morphine equivalents using the molecular weight. Bioavailability of subcutaneous morphine was assumed to be 100 % [ 19 , 20 ]. One- two- and three-compartment models were tested for morphine and its metabolites using the first-order conditional estimation method with interaction (FOCE+I) and the ADVAN5 subroutine.…”

Opioid rotation from transdermal fentanyl to continuous subcutaneous hydromorphone in a cachectic patient: A case report and review of the literature

“… TDF: transdermal fentanyl; MEDD: morphine equivalent daily dose. Standardized opioid conversion factors used in our hospital: a Oral morphine ÷ 2 = parenteral morphine based on chronic oral opioid use 11 and b morphine ÷ 5 = hydromorphone. 12 Alternative ratios used in clinical practice: oral:parenteral morphine 3:1 and morphine:hydromorphone 10:1.5.…”