Pharmacokinetics of Oxycodone After Intravenous and Subcutaneous Administration in Japanese Patients with Cancer Pain

Abstract

In Japan, Oxycodone hydrochloride injection formulation has been approved in 2012. However, its pharmacokinetics has been poorly studied. The aim of this study is to evaluate the pharmacokinetics of oxycodone after intravenous and subcutaneous administration of oxycodone hydrochloride injection in Japanese patients with cancer pain. Noncompartmental analysis and population pharmacokinetic analysis were performed. We conducted a multicenter open-label study of oxycodone hydrochloride administered as constant infusion with the dose titrated individually according to the pain intensity in patients with cancer pain. Pharmacokinetic parameters for plasma oxycodone and its metabolites were estimated using pharmacokinetics of oxycodone was evaluated using a total of 344 plasma concentrations obtained from 89 patients. The estimated geometric mean clearance (CL) of oxycodone was 24.3 L per hour after constant intravenous infusion and 29.5 L per hour after constant subcutaneous infusion, respectively. Population pharmacokinetic analysis indicated that body surface area was the influencing factor on CL and there were no pharmacokinetic differences for CL between intravenous and subcutaneous infusion. These results provide important information for the clinical use of oxycodone injection.

Slow drug delivery decreased total body clearance and altered bioavailability of immediate‐ and controlled‐release oxycodone formulations

“…2014; Kokubun et al. 2014) and goodness of fit of the two‐compartment analyses of the IV data to assess the intrinsic oxycodone distribution and clearance. Solid lines: observed data; dotted lines: model predicted data were shown in Figure 2.…”

“…2002), subcutaneously (s.c.) (Kokubun et al. 2014), bucally (Kokki et al. 2004), rectally (Tegon et al.…”

“…2014; Kokubun et al. 2014). Oxycodone is relatively well absorbed after oral administration, and commercially available IR and ER formulations have a bioavailability of 40–80% (Mandema et al.…”

“…It has been administered intravenously (i.v.) (Takala et al 1997;Kokki et al 2004;Hao et al 2014;Kokubun et al 2014), intramuscularly (i.m.) (Kokki et al 2004), intranasally (i.n.)…”

Pharmacokinetic Bioequivalence Studies of an Extended-Release Oxycodone Hydrochloride Tablet in Healthy Japanese Subjects Under Fasting and Fed Conditions Without an Opioid Antagonist

“…Oxycodone hydrochloride injection formulation was developed as an alternative route for these patients with cancer pain and was approved in 2012. Population PK analysis indicated no PK differences for total body clearance between intravenous and subcutaneous infusion in Japanese patients with cancer pain [9]. …”