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

• DOI: 10.1002/prp2.210
• Publication Date: 2016-02-06T00:02:41Z
• Authors: Yan Li; Duxin Sun; Maria Palmisano; Simon Zhou
• Keywords: NONMEM; ADME

Abstract Oxycodone is a commonly used analgesic with large body of pharmacokinetic data from various immediate‐release or controlled‐release formulations, under different administration routes, and in diverse populations. Longer terminal half‐lives extravascular as compared to IV have been attributed flip‐flop pharmacokinetics the rate constant absorption slower than elimination. However, PK parameters studies showed faster Sustained release formulations guided by concept produced mixed outcomes formulation development clinical studies. This research aims develop mechanistic knowledge oxycodone ADME , provide consistent interpretation diverging results insight guide further extended optimize use oxycodone. human were collected literature digitized. The analyzed using new model Weibull function describe time‐varying drug releases/ oral absorption, elimination dependent upon input portal vein. traditional models coded NONMEM . Sensitivity analyses conducted address relationship between rates release/absorption profiles plus half‐lives. Traditional could not be applied consistently Errors forced on elimination, both when PO fitted separately. total clearance caused adequately describes complex interplay vivo. Terminal phase profile was shown reflect due formulations. Mechanistic functions, rate‐dependent saturable well described kinetics literature. It no actual during phase, but producing appearance offered for modified