Clinical drug investigation
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In patients managed with opioids for chronic pain, opioid-induced bowel dysfunction—specifically, opioid-induced constipation (OIC)—is a common side effect, which has a significant impact on quality of life (QoL). The most recent developments for management of OIC are opioid antagonists, including naloxone, a competitive antagonist of peripheral opioid receptors that reverses opioid-induced peripheral gastrointestinal (GI) effects. A prolonged-release formulation of naloxone is available in combination with oxycodone (OXN PR). ⋯ In patients with moderate-to-severe chronic pain, randomized trials have demonstrated that OXN PR has equal analgesic efficacy and safety, but results in improved bowel function, compared with prolonged-release oxycodone (Oxy PR) alone. In conclusion, randomized studies using the BFI, as well as real-world clinical practice observations, have demonstrated improved QoL for patients taking OXN PR. This combination should allow more patients to benefit from the analgesic efficacy of opioid therapy and should minimize the side effects of constipation that correspond to improvements in QoL and healthcare offsets.
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Randomized Controlled Trial Comparative Study
Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.
A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. ⋯ All three hydrocodone ER tablet prototypes (low-, intermediate-, and high-level polymer coating) demonstrated ER pharmacokinetic characteristics. The hydrocodone ER tablet prototype with the high-level coating was selected for development because of its comparable exposure to the hydrocodone IR/APAP formulation and potentially increased ability to resist rapid drug release upon product tampering because of a higher polymer coating level. All study medications were well tolerated in healthy naltrexone-blocked volunteers.
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Remifentanil has a rapid onset and short duration of action, predictable pharmacokinetic/pharmacodynamic profile, and unlike fentanyl, does not accumulate with repeated or prolonged administration. This study evaluated predictors of remifentanil use in surgical patients with renal or hepatic impairment, or obesity in the United States who received remifentanil, fentanyl, or the combination. ⋯ Remifentanil in combination with fentanyl is used less than fentanyl in surgical patients with hepatic impairment or obesity. This is inconsistent with the fact that the pharmacokinetic/pharmacodynamic features of remifentanil suggest it is the preferred intraoperative opioid in these patients. Predictors of remifentanil use in patients with renal or hepatic impairment, or obesity include older age, obesity, and Medicare as primary payer. Remifentanil in combination with fentanyl was significantly less utilized than fentanyl in persons with Medicaid as primary payer even though there was a disproportionate enrollment of beneficiaries with renal or hepatic disease, or obesity in state Medicaid programs.