Assessment of a formulation designed to be crush-resistant in prescription opioid abusers.

Background: The extent of prescription opioid abuse has led to the development of formulations that are difficult to crush. The purpose of the present studies was to examine whether experienced prescription opioid abusers (individuals using prescription opioids for non-medical purposes regardless of how they were obtained) were able to prepare a formulation of oxymorphone hydrochloride ER 40 mg designed to be crush-resistant (DCR) for intranasal (study 1) or intravenous abuse (study 2), utilizing a non-crush-resistant formulation of oxymorphone (40 mg; OXM) as a positive control.

Methods: No drug was administered in these studies.

The effects of ethanol on the bioavailability of oxymorphone extended-release tablets and oxymorphone crush-resistant extended-release tablets.

Unlabelled: Adverse events may occur with an extended-release (ER) opioid if tampering or coadministration with ethanol causes excessive exposure (dose dumping) to the opioid. The effects of ethanol on the in vitro dissolution and in vivo pharmacokinetics of oxymorphone ER and oxymorphone crush-resistant formulation (CRF) were evaluated. In vitro dissolution rates were measured for oxymorphone ER 40-mg and oxymorphone CRF 40-mg tablets in aqueous solutions of 0 to 40% ethanol.

Bioequivalence of oxymorphone extended release and crush-resistant oxymorphone extended release.

Background: A formulation of crush-resistant extended-release opioids may deter abuse. The purpose of this study was to evaluate the bioequivalence of oxymorphone extended-release (Oxy-ER) and a crush-resistant formulation of oxymorphone extended-release (Oxy-CRF).

Methods: In three open-label, randomized studies, healthy adults at a clinical research center received two single oral doses of Oxy-ER and two single doses of Oxy-CRF, each separated by a ≥7-day washout.

Concurrent induction and mechanism-based inactivation of CYP3A4 by an L-valinamide derivative.

DPC 681 (N-[(3-fluorophenyl)methyl]glycyl-N-[3-[((3-aminophenyl) sulfonyl)-2-(aminophenyl)amino]-(1S,2S)-2-hydroxy-1-(phenyl-methyl)propyl]-3-methyl-l-valinamide) is a potent peptide-like human immunodeficiency virus protease inhibitor that was evaluated in phase I clinical trials. In primary cultures of hepatocytes, DPC 681 significantly induced the testosterone 6beta-hydroxylase activity of rat CYP3A, but not human CYP3A4. Western blot analysis, however, demonstrated a 3-fold increase in expression of CYP3A4 protein by 20 microM DPC 681 in primary cultures of human hepatocytes.

Hepatic but not intestinal CYP3A4 displays dose-dependent induction by efavirenz in humans.

Objective: The capacity of the non-nucleoside reverse transcriptase inhibitor efavirenz to induce either liver CYP3A4 or intestinal CYP3A4, or both, as well as intestinal P-glycoprotein, was evaluated in healthy volunteers during and after a 10-day treatment course with two different daily doses.

Methods: Cohorts of 12 healthy subjects were randomized (2:1) to receive either efavirenz or placebo orally for 10 days. The first cohort received 200 mg efavirenz and the second cohort received 400 mg efavirenz daily.

Lack of Pharmacokinetic Interaction between Aspirin and Warfarin.

An open-label, randomized, two-phase crossover study was conducted on 36 healthy male volunteers to identify the effects of coadministration of aspirin (acetylsalicylic acid; ASA) and crystalline warfarin sodium (Coumadin((R))) on the elimination and disposition kinetics of ASA, salicylic acid (SA) and R- and S-warfarin enantiomers. Twenty-four subjects were administered single doses of 325 mg of ASA alone and in combination with 10 mg of crystalline warfarin sodium with a 1-week washout between ASA doses. ASA and SA pharmacokinetic parameters were determined after each dose.