Intravenous Abuse Research Articles

A Single-Dose, 3-Way Crossover Pharmacokinetic Comparison Between Immediate-Release Oxycodone Hydrochloride With Aversion Technology (IRO-A, Oxecta), IRO-A With Niacin, and Oxycodone Hydrochloride (Roxicodone) in Healthy Adults Under Fasting Conditions

Snorting and intravenous use are common routes of administration for advanced opioid abusers. A tablet form of immediate-release oxycodone (IRO) developed using Aversion Technology combines immediate release (IR) oxycodone HCl with inactive functional excipients that are intended to discourage tampering associated with intranasal and intravenous abuse (IRO-A; Oxecta, Pfizer). The purpose of this single-dose, open-label, randomized, 3-period, 3-treatment crossover study was to evaluate the bioequivalence of IRO-A to the marketed immediate-release oxycodone HCl (IRO; Roxicodone, Xanodyne Pharmaceuticals Inc., Newport, KY). IRO-A was also compared with IRO-A with niacin, a product previously developed containing the same functional excipients plus niacin as an aversive agent to discourage oral overconsumption. Healthy adults (N = 40) aged 18-55 years received single 15-mg doses of IRO-A, IRO-A with niacin (60 mg), or IRO after fasting overnight. Naltrexone was administered to diminish opioid effects. Doses were separated by a ≥7-day washout. Plasma samples taken at designated time points were analyzed using liquid chromatography with tandem mass spectrometry. Geometric mean ratios for ln-transformed parameters for IRO-A and IRO were 92%, 104%, and 104% for Cmax, AUClast (AUC is area under the concentration-time curve), and AUCinf; 90% confidence intervals were within the accepted 80%-125% range. IRO-A was also bioequivalent to IRO-A with niacin. Adverse events were mild to moderate in intensity and typical of opioid therapy (nausea, headache, vomiting). Flushing only occurred when the subjects received the IRO-A with niacin treatment (9/37 subjects). The results demonstrated that IRO-A is bioequivalent to IRO and IRO-A with niacin. With features designed to discourage tampering associated with common forms of abuse, IRO-A may provide an alternative to conventional immediate-release oxycodone formulations.

The impact of a reformulation of extended-release oxycodone designed to deter abuse in a sample of prescription opioid abusers

BackgroundPrescription opioid abuse is a significant public health concern that requires strategies to reduce its impact, including development of abuse deterrent formulations. OxyContin®, an extended-release oxycodone (ERO) formulation, has been widely abused. This study assessed the effects of reformulated ERO, designed to be more difficult to manipulate for purposes of intranasal and intravenous abuse, on patterns of opioid abuse among a sample of individuals from rural Appalachia with a history of ERO abuse. MethodsStructured interviews assessing opioid abuse (past 30-day abuse and retrospectively reported abuse prior to the reformulation in August 2010) were completed by 189 individuals between December 2010 and September 2011. ResultsThe past 30-day prevalence and frequency of reformulated ERO abuse through any route (33%, 1.9 days/month), snorting (5%, 0.2 days/month), and injecting (0.5%, <0.1 days/month) were low and infrequent compared to that of IR oxycodone (any route: 96%, 19.5 days/month; snorting: 70%, 10.3 days/month; injecting: 51%, 10.5 days/month) and retrospectively reported abuse of original ERO in August 2010 (any route: 74%, 13.4 days/month; snorting: 39%, 6.0 days/month; injecting: 41%, 8.6 days/month). After the reformulation, the prevalence of original ERO abuse significantly declined while abuse of reformulated ERO remained steadily low. Heroin abuse was rare in this sample. ConclusionsIn this sample, abuse of reformulated ERO was low, and lower than abuse of original ERO retrospectively and IR oxycodone concurrently, particularly through injecting and snorting routes of administration. There was no evidence to suggest that reformulated ERO became a substitute for original ERO.

Thrombotic Microangiopathy Associated with Intravenous Injection of Opana ER®: University Medical Center Case Series

In response to the rapidly rising intravenous opioid abuse epidemic, the United States Food and Drug Administration is currently promoting the development of prescription opioid tablets that are specifically formulated to deter abuse.

Pulmonary Foreign Body Embolism and Granulomatosis in Intravenous Substance Abuse

Prescription drug abuse has increased in the United States in part because of the relative ease of acquisition. Some drug abusers resort to the injection of crushed tablets for rapid onset and increased euphoria. Adolescents and young adults with chronic pain disorders and intravenous access ports are particularly susceptible to this practice. Clinically, those who inject tablets may develop dyspnea, hypoxemia, pulmonary hypertension, and are at an increased risk of sudden death. In addition to the active ingredient(s), pharmaceutical tablets contain inert excipients such as talc, starch, microcrystalline cellulose and crospovidone. Angiothrombosis and foreign body granulomatosis induced by particulate emboli are the major pathological findings identified. Tablet excipients can be discerned by their morphological and histochemical attributes. Microanalytic techniques may be required for definitive identification. Inhalational exposures, aspiration, endogenously formed crystals, and hyperalimentation are potential mimickers of tablet-induced foreign body emboli and granulomatosis.

Plasma Exchange Is Not Necessary For The Treatment Of Microangiopathic Hemolytic Anemia Due To Intravenous Opana Abuse

Thrombotic Thrombocytopenic Purpura (TTP) is known to have a deficiency of ADAMTS13 as a feature with very low-to-absent activity as a hallmark of a distinct set of patients with an acquired microangiopathic hemolytic anemia. The working definition for TTP we utilize is a thrombotic microangiopathy and severe ADAMTS13 deficiency which results in the accumulation of ultra large multimers of von Willebrand protein, which results in an aggregation of platelets producing microvascular occlusion and causing some of the “classical” symptoms of TTP including thrombocytopenia, neurologic symptoms, and renal dysfunction. The treatment for acquired TTP is plasma exchange which is believed to replace the deficient ADAMTS13 and remove anti-ADAMTS13 auto-antibodies. While having demonstrated survival benefit for treatment of TTP, other microangiopathies such as Hemolytic Uremic Syndrome (HUS) do not share the same success. In January 2013, the CDC reported a TTP-like illness associated with intravenous use of Opana (an extended release oxymorphone). This was initially identified in rural Tennessee. A total of 15 patients were reported. Fourteen of the fifteen patients had reported abusing IV Opana. The median time before presentation of injecting Opana was 1 day with a range of 0-2 days before hospital admission. Twelve of the fifteen patients were treated with plasma exchange. ADAMTS13 was reported on eight of the patients with a range of 84-131% without concurrent infection and 42-199% with concurrent infection. Twelve of the fifteen patients reported chronic Hepatitis C infection or had a positive result during hospital admission. We report a new series of 11 patients from two rural communities in North Carolina admitted to the hospital with suspicion of TTP. Microangiopathy was confirmed on visualization of peripheral blood films. While we report similar findings compared to the CDC report, we also have demonstrated the ability to withhold plasma exchange in such patients reporting IV Opana use. Although recovery time was variable, improvement in symptoms occurred by withholding the offending agent (IV Opana) and providing supportive care without the use of therapeutic plasma exchange. Our patients ranged in age from 22- 50 years old, 6 males and 5 females, all Caucasian. All of the patients reported recent intravenous Opana abuse (0-5 days prior to presentation). Five were treated initially for sepsis, 3 with generalized pain (chest, back), and all had anemia. Platelet counts ranged from 28,000-121,000/mm3 (mean 66,000/mm3), 9 of the 11 were diagnosed with concurrent Hepatitis C although only 1 knew of prior infection. ADAMTS13 activity ranged from 38-119% with a mean of 65%. While the specific etiology of intravenous Opana induced microangiopathic hemolytic anemia (MAHA) is unclear, our experience has demonstrated that withholding therapeutic plasma exchange is an acceptable approach to MAHA of this etiology. Though plasma exchange is standard care for TTP, it does not appear to be necessary for treatment of drug induced MAHA related to intravenous Opana use in the absence of markedly deficient ADAMTS13. At our institution the utilization of a rapid assay for ADAMTS13 has resulted in its use as a reliable biomarker for diagnosis of TTP related to anti-ADAMTS13 autoantibodies as opposed to MAHA related to other causes, such as the emerging trend of intravenous Opana use. Withdrawal of the offending agent without the use of therapeutic plasma exchange appears to be an acceptable approach to this specific disorder. Disclosures: No relevant conflicts of interest to declare.

Disaccharides in Urine Samples as Markers of Intravenous Abuse of Methadone and Buprenorphine

Methadone and buprenorphine are commonly used as oral substitutes in opiate maintenance programs to treat persons who are dependent on heroin. During these programs, patients are not allowed to continue using illicit drugs. Abstinence can easily be monitored by urine tests with immunochemical methods. It is well known that the intravenous abuse of heroin substitutes like methadone or buprenorphine has become common as well. The methadone-prescribing physician has no opportunity to check whether the opiate maintenance treatment patient takes his substitution medicines orally as intended or continues with his intravenous misuse now substituting the methadone instead of injecting heroin. In Germany, substitutes are available as liquids and tablets that contain carbohydrates as adjuvants. Sucrose is used to increase viscosity in liquids, while lactose is needed for pressing tablets (e.g., Methaddict® and Subutex®). In case of oral ingestion, disaccharides are broken down into monosaccharides by disaccharidases in the small intestine. These monosaccharides are absorbed into the blood stream by special monosaccharide transporters. Disaccharidases do not exist in blood, thus sucrose and lactose are not split if substitute medicines are injected intravenously. Our assumption, therefore, was that they are excreted unchanged in urine. We investigated a method for the detection of disaccharides in urine as markers of intravenous abuse of substitutes. Urine samples of 26 intravenous substitute abusers showed all positive results for lactose (76.9%) and/or sucrose (73.1%). The method is assumed to be useful to detect intravenous abuse of substitutes.

Intravenous Abuse of Methylphenidate

Intravenous Abuse of Methylphenidate

The outcome of the movement disorder in methcathinone abusers: clinical,MRIand manganesemia changes, and neuropathology

There is limited knowledge regarding the long-term outcome of the methcathinone/manganese-induced movement disorder. Our purpose was to define prognosis in intravenous methcathinone abusers affected by this distinctive disorder attributed to manganese (Mn) toxicity. Also, neuropathology from a globus pallidus region biopsy from a former user is reported. Eighteen methcathinone abusers were categorized as active (five), discontinued (four) or former (nine) users. They were reassessed after a median of 32.5 months (range 3.4-59.6) clinically, on rating scales, and with MRI and blood Mn levels. The biopsy was examined ultrastructurally. Overall the group showed a slight tendency to deterioration at follow-up on clinical assessment of motor functioning, especially the active users. No significant change occurred on parkinsonian rating scale reassessment. Significant reduction in Mn levels occurred in former users, and decreased T1-weighted hyperintensity on basal ganglia MRI occurred in 3 of 4 former and 2 of 3 discontinued users, despite lack of clinical improvement. The biopsy consisted of white matter showing decompacted myelin sheaths and frequent abnormalities of mitochondria. No improvement in this Mn-induced movement disorder occurs after cessation of methcathinone abuse despite improvement of Mn blood levels and/or MRI abnormalities. Ultrastructural abnormalities in a former user confirm structural damage to white matter is associated with the disorder. Methcathinone/Mn toxicity is an important, disabling and permanent medical sequel of intravenous drug abuse in the former Soviet Union.

Thrombotic Thrombocytopenic Purpura (TTP)–Like Illness Associated With Intravenous Opana ER Abuse—Tennessee, 2012

Thrombotic Thrombocytopenic Purpura (TTP)–Like Illness Associated With Intravenous Opana ER Abuse—Tennessee, 2012

Femoral vein obturator bypass revascularization in groin infectious bleeding: two case reports and review of the literature

IntroductionGroin infections resulting in arterial bleeding due to bacterial vessel destruction are a severe challenge in vascular surgery. Patients with them most often present as emergencies and therefore need individualized reconstruction solutions.Case presentationCase 1 is a 67-year-old man with infectious bleeding after an autologous reconstruction of the femoral bifurcation with greater saphenous vein due to infection of a bovine pericard patch after thrombendarterectomy. Case 2 is a 35-year-old male drug addict and had severe femoral bleeding and infection after repeated intravenous and intra-arterial substance abuse. Both patients were treated with an autologous obturator bypass of the superficial femoral vein. We review the current literature and highlight our therapeutic concept of this clinical entity.ConclusionsTreatment should include systemic antibiotic medication, surgical control of the infectious site, revascularization and soft tissue repair. An extra-anatomical obturator bypass with autologous superficial femoral vein should be considered as the safest revascularization procedure in infections caused by highly pathogenic bacteria.

A comparison among tapentadol tamper‐resistant formulations (TRF) and OxyContin® (non‐TRF) in prescription opioid abusers

To examine whether tamper-resistant formulations (TRFs) of tapentadol hydrochloride extended-release (ER) 50 mg (TAP50) and tapentadol hydrochloride 250 mg (TAP250) could be converted into forms amenable to intranasal (study 1) or intravenous abuse (study 2). Randomized, repeated-measures study designs were employed. A non-TRF of OxyContin® 40 mg (OXY40) served as a positive control. No drug was taken in either study. The studies took place in an out-patient setting in New York, NY. Twenty-five experienced, healthy ER oxycodone abusers participated in each study. The primary outcome for study 1 was the percentage of participants who indicated that they would snort the tampered tablets, while the primary outcome for study 2 was the percentage yield of active drug in solution. Other descriptive variables, such as time spent manipulating the tablets, were also examined to characterize tampering behaviors more clearly. Tampered TRF tablets were less desirable than the tampered OXY40 tablets. Few individuals were willing to snort the TRF particles (TAP50: 24%, TAP250: 16%; OXY40: 100% P < 0.001). There was less drug extracted from the TAP50 tablet than from the OXY40 tablet (3.52 versus 37.02%, P = 0.008), and no samples from the TAP250 tablets contained analyzable solutions of the drug. It took participants longer to tamper with the TAPs (study 1: TAP50 versus OXY40, P < 0.01; TAP250 versus OXY40, P < 0.01; study 2: TAP250 versus OXY40, P < 0.05). Tamper-resistant formulations of taptentadol (pain relief) tablets do not appear to be well-liked by individuals who tamper regularly with extended-release oxycodone tablets. Employing tamper-resistant technology may be a promising approach towards reducing the abuse potential of tapentadol extended-release.

CPC-149 Trimebutine: A Case of Abuse and Possible Dependence

BackgroundTrimebutine has an agonist effect on digestive tract and brain mu, kappa, and delta opiate receptors.Purpose To describe a case report of an abuse and a possible dependence on trimebutine.Materials...

Polymicrobial Endocarditis in Intravenous Heroin and Fentanyl Abuse

Infective endocarditis is a life threatening condition with a high mortality rate. Intravenous Drug Abusers (IVDA) are more likely to acquire endocarditis. Most of the cases of infective endocarditis are caused by a single pathogen; cases of polymicrobial endocarditis are rare and they are associated with a reported mortality rate of more than 30%. Only 21 cases of N. sicca endocarditis have been described in the literature since 1918, and only 15 reported cases of endocarditis which involved Actinomyces species have been reported since 1939. We are reporting a case of a 49-year-old male with intravenous heroin and fentanyl abuse, who presented with infective endocarditis caused by Neisseria sicca/subflava(N. sicca), Actinomyces, Streptococcus mitis, and Haemophilus parainfluenzae, complicated by septic emboli to the lungs and skin, ARDS , splenic infarct and immunocomplex mediated proliferative glomerulonephritis.

Shear-Thinning Rheology of the Abuse-Deterrent Dosage Form Extracts

Prescription drug abuse has become a worldwide public health issue. Of particular concern is the dose-dumping effect caused by co-ingestion of ethanol which leads to premature rapid release of the drug load. Also, medications can be crushed and dissolved in ethanol for extraction to allow for parenteral routes of administration. To combat this abuse, the pharmaceutical industry has begun to develop dosage forms that are abuse deterrent. In this study, we investigated the use of a cone-and-plate rheometer to evaluate the rheological properties of polyethylene oxide (a common excipient in abuse deterrent dosage forms) in water-alcohol mixtures. This polymer prevents rapid drug dissolution in alcohol by forming a viscous gel in the presence of solvents to discourage intravenous abuse. Our results showed that 2% w/v polyethylene oxide in hydro-alcoholic solvents behaved non-Newtonian. Rheograms showed a non-linear profile where apparent viscosity was decreased as a function of increasing shear rate, and was fit to a Herschel-Bulkley fluid model. The greater viscosities seen in test solutions at low shear rates may prevent rapid ethanol dissolution of drug, and provide difficulty when dissolving a product in hydro-alcoholic solutions. However, high shear rates such as that seen in rapid mixing or in a needle and syringe are likely to adversely affect the deterrence capacity of polyethylene oxide in solutions.

Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans

BackgroundPrescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine. MethodsPlasma was collected for 72h after administration of placebo or 2, 4, 8, 12, or 16mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography–tandem mass spectrometry with limits of quantitation of 0.1μg/L. ResultsMaximum buprenorphine concentrations (mean±SE) were detected 10min after 2, 4, 8, 12, 16mg IV: 19.3±1.0, 44.5±4.8, 85.2±7.7, 124.6±16.6, and 137.7±18.8μg/L, respectively. Maximum norbuprenorphine concentrations occurred 10–15min (3.7±0.7μg/L) after 16mg IV administration. ConclusionsBuprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2–16mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12mg.

Asymptomatic spleen rupture in patient with endocarditis

A 50-year-old Caucasian male presented to the emergency department with worsening abdominal pain more than 6 h associated with nausea and dizziness. The pain was dull in nature periumbilical with no radiation. He denied hematemesis, hematochezia, trauma, fever or change in urine/bowel habits. Past medical history was positive for diabetes, hypertension and intravenous (IV) heroin abuse. On arrival, he was lethargic and vital signs were remarkable for sinus tachycardia 122 per min, 61/40 mm Hg blood pressure and respiratory rate of 25 cycles per minute. Abdominal examination showed generalized tenderness more prominent in the left upper quadrant with no rebound. Apart from faint …

Randomized, double-blind, placebo-controlled and active-controlled study to assess the relative abuse potential of oxycodone HCl-niacin tablets compared with oxycodone alone in nondependent, recreational opioid users

BackgroundAbuse-deterrent formulations attempt to address public health and societal concerns regarding opioid abuse. Oxycodone HCl-niacin tablets combine oxycodone HCl with niacin and functional inactive excipients to create potential barriers to oral, intranasal, and intravenous abuse. This study compared the relative abuse potential of oral immediate-release oxycodone HCl-niacin with that of oral immediate-release oxycodone HCl and placebo in nondependent, recreational opioid users.MethodsForty-nine participants received oxycodone HCl-niacin 40/240 mg and 80/480 mg, oxycodone 40 mg and 80 mg, and placebo in a randomized, double-blind, placebo-controlled and active-controlled, five-way crossover study. Primary endpoints based on a bipolar 100 mm visual analog scale for drug liking were area under effect curve (AUE0–1h, AUE0–2h, AUE0–3h), peak disliking, and effect at 0.5 hours post-dose (E0.5h). Other endpoints included take drug again assessment, overall drug liking, and pupillometry.ResultsThere were statistically significant differences between oxycodone HCl-niacin and oxycodone HCl doses for all primary endpoints (P < 0.0001, all comparisons), suggesting reduced abuse potential with oxycodone HCl-niacin. Take drug again and overall drug liking showed greater liking of oxycodone alone. Oxycodone HCl-niacin 80/480 mg had consistently lower liking assessments than oxycodone HCl-niacin 40/240 mg, suggesting a dose-response to the aversive effects of niacin. Opioid-related adverse events were similar for equivalent oxycodone doses. The treatment-emergent adverse events most specifically associated with oxycodone HCl-niacin (ie, skin-burning sensation, warmth, and flushing) were consistent with the expected vasocutaneous effects of niacin. No serious adverse events were reported.ConclusionOxycodone HCl-niacin tablets may, in a dose-dependent manner, decrease the potential for oral abuse of oxycodone without unexpected adverse events or clinically signifi-cant differences in safety parameters compared with oxycodone alone. Although statistically powered, the small size of the study sample and the characteristics of its participants may not be generalizable to the population that abuses prescription opioid medications.

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

BackgroundThe 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 40mg designed to be crush-resistant (DCR) for intranasal (Study 1) or intravenous abuse (Study 2), utilizing a non-crush-resistant formulation of oxymorphone (40mg; OXM) as a positive control. MethodsNo drug was administered in these studies. Participants were provided with DCR and OXM tablets in random order and asked to prepare them for abuse with tools/solutions that they had previously requested. The primary outcome for Study 1 was particle size distribution, and the primary outcome for Study 2 was percent yield of active drug in the extracts. Other descriptive variables were examined to better understand potential responses to these formulations. ResultsFewer DCR than OXM particles were smaller than 1.705mm (9.8% vs. 97.7%), and thus appropriate for analyses. Percent yield of active drug in extract was low and did not differ between the two formulations (DCR: 1.95%; OXM: 1.29%). Most participants were not willing to snort (92%) or inject (84%) the tampered products. Participants indicated that they found less relative value in the DCR than the OXM formulation across both studies. ConclusionsThese data suggest that the oxymorphone DCR formulations may be a promising technology for reducing opioid abuse.

Dose Proportionality and the Effects of Food on Bioavailability of an Immediate-Release Oxycodone Hydrochloride Tablet Designed to Discourage Tampering and Its Relative Bioavailability Compared With a Marketed Oxycodone Tablet Under Fed Conditions: A Single-Dose, Randomized, Open-Label, 5-Way Crossover Study in Healthy Volunteers

BackgroundAn immediate-release oxycodone hydrochloride formulation (IRO-A) indicated for moderate to severe pain was designed (by adding functional excipients) to discourage tampering associated with intranasal and intravenous abuse of prescription opioids. ObjectivesThe primary objective of this study was to determine the dose proportionality of oxycodone in IRO-A tablets under fasted conditions. Secondary objectives were to assess food effects on the pharmacokinetics of IRO-A tablets, to compare the relative bioavailability of oxycodone in IRO-A tablets versus marketed oxycodone hydrochloride (IRO) tablets under fed conditions and to evaluate the single-dose safety profile of the IRO-A tablets in healthy volunteers pretreated with naltrexone. MethodsThis open-label, single-dose, randomized, 5-way crossover study was conducted in healthy adults who received each of the following treatments, separated by a washout period of ≥7 days: IRO-A 1 × 5 mg, 2 × 5 mg, and 2 × 7.5 mg under fasted conditions, and IRO-A 2 × 7.5 mg and IRO 1 × 15 mg after a high-fat, high-calorie breakfast. Naltrexone was administered to minimize untoward pharmacologic effects of oxycodone. Dose proportionality (IRO-A), food effects (IRO-A), and relative bioavailability in a fed state (IRO-A and IRO) were assessed by using bioequivalence criteria (90% CIs between 80% and 125% for Cmax and AUC). ResultsOf the 35 adults enrolled in the study, 33 completed at least 1 dosing period. Most participants were male (54%) and white (69%), with a mean (SD) age of 32.6 (11.1) years and mean weight of 75.5 (12.3) kg. Plasma levels of oxycodone in IRO-A suggested dose-proportional pharmacokinetics; 90% CIs for dose-normalized Cmax, AUC0–last, and AUC0–∞ fell within the 80% to 125% range. Concomitant food intake with IRO-A resulted in an ∼14% reduction in oxycodone Cmax and an ∼21% increase in AUC0–last. The bioavailability of oxycodone from IRO-A tablets in the fed state was comparable with IRO tablets based on AUC parameters, although Cmax was ∼16.5% lower. Reported or observed treatment-emergent adverse events were monitored throughout the study and were similar for IRO-A and IRO tablets. Nausea, headache, abdominal pain, and dizziness were the most common and are consistent with known effects of oxycodone after naltrexone blockade. ConclusionsPlasma levels of oxycodone in IRO-A tablets were compatible with proportional single-dose pharmacokinetics from 5 to 15 mg under fasted conditions. Administration of IRO-A with food suggested increased overall bioavailability relative to fasting conditions and a reduction in peak systemic exposure of oxycodone that is not expected to be clinically significant. When comparing IRO-A tablets with IRO tablets in the fed state, the overall systemic exposure of oxycodone was comparable, and peak systemic exposure was lower. ClinicalTrials.gov identifier: NCT01530542.

Talcum induced pneumoconiosis following inhalation of adulterated marijuana, a case report

BackgroundTalcosis, a granulomatous inflammation of the lungs caused by inhalation of talcum dust, is a rare form of pneumoconiosis. Besides inhalative occupational exposure, intravenous abuse of adulterated drugs is a major cause for this condition. Minerals such as talcum (magnesium silicate) and sand (predominant silicon dioxide) are used to increase both volume and weight of illicit substances. In intravenous heroin-abuse, talcosis is a well-known complication. Here we describe a case of talcosis caused by inhalative abuse of adulterated marijuana.Clinical historyA 29-year old man presented with persistent fever, dyspnea and cervical emphysema. He admitted consumption of 'cut' marijuana for several years, preferentially by water pipe smoking.Morphologic findingsLung-biopsies showed chronic interstitial lung disease, anthracotic pigments and birefringent material. Energy dispersive x-ray spectroscopy revealed silicon-containing particles (1-2 μm) and fine aluminum particles (< 1 μm), magnesium and several other elements forming a spectrum compatible with the stated water pipe smoking of talcum-adulterated marijuana.ConclusionsThe exacerbated chronic interstitial lung disease in a 29-year old patient could be attributed to his prolonged abuse of talcum-adulterated marjuana by histopathology and x-ray spectroscopy. Since cannabis consumption is widely spread among young adults, it seems to be justified to raise attention to this form of interstitial pulmonary disease.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnomx.eu/vs/krause/html/start.html.