Liposolubility and Protein Binding of Oxycodonein Vitro

Publisher Website
Google Scholar
Abstract
The liposolubility and protein‐binding of oxycodone were studiedin vitroand compared with other opioids. Liposolubility was assessed by three different methods: 1) the shake‐flask method with n‐octanol at pH 4‐9, 2) measuring the retention time in reversed‐phase high‐performance liquid chromatography (RP‐HPLC) with a LiChrosorb® RP‐18 and 3) studying the solubility in human epidural and subcutaneous fat. Human fat was obtained from patients undergoing surgery for herniated intervertebral disc. After incubation, pieces of fatty tissue immersed in a buffer solution containing oxycodone, morphine, pethidine or fentanyl for 10‐40 min.; tissue pieces were homogenated, opioids extracted and opioid concentrations measured by gas‐ and high‐performance liquid chromatography. The binding of oxycodone, morphine and fentanyl in plasma proteins was studied by ultrafiltration (Amicon®‐kit). The mean apparent partition coefficients Pappof oxycodone, morphine, pethidine and fentanyl in n‐octanol at pH 7 were 0.7, 0.5, 10.5 and 399, respectively. The retention times in RP‐HPLC for oxycodone, morphine, pethidine, fentanyl and buprenorphine were 0.6 min., 0.2 min., 2.4 min., 2.3 min. and 10.5 min., respectively. Only buprenorphine and fentanyl appeared to be highly lipophilic in the human fat tissue experiments; no difference was found between epidural or subcutaneous fat in this respect. Thein vitroprotein binding of oxycodone was 38%, of morphine 31% and of fentanyl 87% in average. It is concluded that, in terms of physicochemical properties, liposolubility and protein‐binding, oxycodone resembles morphine more than it does fentanyl.