Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.

The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions. Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis, and a two-factor model was used to assess for dose and sex differences. The mean ± SEM oral cocaine bioavailability was 0.32 ± 0.04 after 100 and 0.45 ± 0.06 after 200 mg oral cocaine. Volume of distribution (Vd) and clearance (CL) were both greatest after 100 mg oral (Vd = 4.2 L/kg; CL = 116.2 mL/[min kg]) compared to 200 mg oral (Vd = 2.9 L/kg; CL = 87.5 mL/[min kg]) and 40 mg IV (Vd = 1.3 L/kg; CL = 32.7 mL/[min kg]). Oral cocaine area-under-thecurve (AUC) and peak concentration increased in a dose-related manner. AUC metabolite-to-parent ratios of benzoylecgonine and ecgonine methyl ester were significantly higher after oral compared to IV administration and highest after the lower oral dose. In addition, minor metabolites were detected in higher concentrations after oral compared to IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile. Cocaine bioavailability values were similar to previous estimates. Oral cocaine also produced a unique metabolic profile, with greater concentrations of major and minor metabolites.

Epidemic Fentanyl Deaths in Maryland: A Public Health Intervention Involving Geographic Information Systems and Collaboration with the Drug Enforcement Administration.

An ongoing epidemic of illicit fentanyl overdose deaths started in Maryland in July 2013. The records of the Office of the Chief Medical Examiner for the state of Maryland were searched to identify these deaths from July 2013 to February 2015. A geographic information system was used to map and analyze the spatial and temporal distribution of the deaths in Maryland. A total of 266 fentanyl-related deaths were identified. The number of deaths per month generally increased from July 2013 to June 2014, decreased precipitously in August 2014, and rose steadily until the end of the study in February 2015. Deaths began in Baltimore City and then spread throughout the state. A statistically significant cluster ("hot spot") of deaths was centered in Baltimore City. Greater death densities were also centered on other cities. A high-density band of deaths extended from Baltimore City towards Annapolis. Deaths extended past cities and into the surrounding suburbs; this effect was most pronounced around Baltimore City. Deaths in Baltimore City appeared concentrated in certain neighborhoods. However, the activity moved between various neighborhoods over the course of the study. Review of the above data with the United States Drug Enforcement Administration's Baltimore Office (DEA) allowed some of the above trends to be explained in terms of illicit drug production, transportation and distribution. The DEA is implementing a new strategy to combat illicit narcotic distribution and use in Maryland.

Methylenedioxypyrovalerone ("bath salts"), related death: case report and review of the literature.

Cathinone derivatives (bath salts) have emerged as the latest drugs of abuse. 3,4-methylenedioxypyrovalerone (MDPV) is the primary active ingredient in bath salts used in this country. This article presents the second reported cause of death by MDPV intoxication alone. In April 2011, a delusional man was emergently brought to a hospital, where he self-reported bath salt usage. He became agitated, developed ventricular tachycardia, hyperthermia, and died. Comprehensive alcohol and drug testing was performed. Using the alkaline drug screen, heart blood contained 0.7 mg/L MDPV and peripheral blood contained 1.0 mg/L MDPV. His bizarre behavior with life-threatening hyperthermia was consistent with an MDPV-induced excited delirium state. MDPV is not yet found by routine immunoassay toxicology screens. Testing for MDPV should be considered in cases with a history of polysubstance abuse with stimulant type drugs, report of acute onset of psychogenic symptoms, excited delirium syndrome, or presentation in a hyperthermic state.

Anaphylaxis after the injection of buprenorphine.

Cause of death rulings in cases when the concentration of a drug or drugs is higher than observed following therapeutic use are generally straightforward "drug deaths." However, when toxicology testing identifies drug concentrations consistent with therapeutic use or detects no drugs at all, then the cause of death determination is more complicated. Given the rapidity and protean manifestations of anaphylaxis, it should be considered in deaths where no other cause of death is apparent in a suspected drug death. This article reports two cases where an anaphylactic reaction was observed following either the actual or alleged use of therapeutic formulations of buprenorphine intravenously.

A fatality from sevoflurane abuse.

A case is presented of a 47-year-old man who died as a result of sevoflurane abuse. Sevoflurane was identified and confirmed by headspace gas chromatography-mass spectrometry. The heart blood sevoflurane concentration was 16 mg/L, and the peripheral blood sevoflurane concentration was 8.0 mg/L. No drugs or other volatile substances were found in the heart blood. The medical examiner ruled that the cause of death was cardiac arrhythmia due to sevoflurane toxicity. Cardiomegaly was listed on Part II of the death certificate. The manner of death was undetermined.

Distribution of phencyclidine into vitreous humor.

Vitreous humor is a fluid contained in the eye that is largely composed of water. The advantages of vitreous humor as a specimen for postmortem drug analysis include its relatively low susceptibility to contamination and the ability to analyze vitreous humor with little or no pretreatment. The postmortem analysis of ethanol in vitreous humor has been well established. However, studies of drug disposition into vitreous humor are limited. Heart blood, subclavian blood, and vitreous humor specimens from 26 phencyclidine-positive postmortem cases were analyzed to evaluate the distribution of phencyclidine into vitreous humor. Phencyclidine intoxication was not the cause of death in any of the cases analyzed. Specimens were analyzed by solid-phase extraction followed by gas chromatography-mass spectrometry. All positive blood specimens were associated with a positive vitreous humor specimen. On average, the blood phencyclidine concentrations were greater than the vitreous humor phencyclidine concentrations, with average blood/vitreous ratios of 2.85 for heart blood and 2.51 for subclavian blood. However, there was considerable variability between cases, which indicates that although vitreous humor is an appropriate specimen for the detection of phencyclidine in postmortem cases, its interpretative value is limited.

Distribution of ether in two postmortem cases.

Diethyl ether (ether) is a volatile liquid that was used in the 1800s as an anesthetic agent; however, it is no longer used for this purpose, partly because of its odor and flammability. Two postmortem cases in which ether was detected are presented. The first case was an 18-year-old male found hanging from a basement ceiling brace in a semi-sitting position with a gas mask covering his face. A container of Prestone starting fluid and a bong were found on the floor close to the body. The second case was a 20-year-old male found unresponsive in his dormitory room with two black plastic trash bags secured over his head. Two saturated rags and a resealable bag containing a clear liquid were contained within these trash bags. An almost empty can of Tradco starting fluid was also found at the scene. Ether concentrations were determined by headspace gas chromatography-mass spectrometry in the selective ion monitoring mode. In case #1, the medical examiner ruled that the cause of death was asphyxia due to hanging; the manner of death was undetermined. In case #2, the medical examiner ruled that the cause of death was asphyxia and the manner of death was suicide.