Analgesia and serum assays of controlled-release dihydrocodeine and metabolites in cancer patients with pain.

Aim of the study was to assess dihydrocodeine (DHC) and metabolites concentrations and their correlations with DHC analgesia in cancer patients with pain. Thirty opioid-naive patients with nociceptive pain intensity assessed by VAS (visual analogue scale) > 40 received controlled-release DHC as the first (15 patients, 7 days) or as the second opioid (15 patients, 7 days). Blood samples were taken on day 2, 4 and 7 at each study period. DHC and its metabolites were assayed by HPLC. DHC provided satisfactory analgesia when administered as the first or the second opioid superior to that of tramadol. When DHC was the first opioid administered, DHC and dihydrocodeine-6-glucuronide (DHC-6-G) concentrations increased in the second and the third comparing to the first assay. A trend of nordihydromorphine (NDHM) level fall between the first and the third assay was noted; trends of dihydromorphine (DHM) level increase in the second relative to the first determination and decrease in the third compared to the second assay were observed. When DHC followed tramadol treatment a trend of DHC concentration increase in the second relative to the first assay was noted. DHC-6-G level increased in the second and in the third comparing to the first determination; NDHM and DHM concentrations were stable. DHC and DHC-6-G concentrations increased similarly during both treatment periods which suggest their prominent role in DHC analgesia. Few significant correlations were found between DHC dose, DHC and metabolites serum concentrations with analgesia suggesting the individual DHC dose titration.