Excretion Profile of Opiates in Dependent Patients in Relation to Route of Administration and Type of Drug Measured in Urine with Immunoassayby E. Taracha, B. Habrat, K. Chmielewska, H. Baran-Furga

Journal of Analytical Toxicology

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Text

Journal of Analytical Toxicology, Vol. 29, January/February 2005

Excretion Profile of Opiates in Dependent Patients in

Relation to Route of Administration and Type of Drug

Measured in Urine with Immunoassay

Ewa Taracha 1,*, Bogusiaw Habrat 2, Karina Chmielewska 2, and Helena Baran-Furga 2 1Department of Neurochemistry, Institute of Psychiatry and Neurology, Warsaw, Poland and 2Department ofPrevention and

Treatment of Substance Dependence, Institute of Psychiatry and Neurology, Warsaw, Poland

Abstract I

It is accepted that opiates are detectable in urine within three days from the last dose at a cut-off value of 300 ng/mL. In our clinical practice, some patients tested positive for morphine even after a week of detoxification. The present study evaluates the time course of opiate excretion in urine of dependent subjects (Fll.25 according to ICD-10)in relation to route of administration and a kind of street heroin. The group comprised 71 men treated for opiate dependency: 33 of them used heroin exclusively b inhalation; 26 i.v.; 12 used i.v. homemade poppy straw decoctions.

Opiate levels were measured once a day by fluorescence polarization immunoassay (TDx Abbott). Detection time ranged from 3 to 10 days for cut-off value 300 ng/mL and from less than one up to seven days for cut-off value 2000 ng/mL. The increases in urine drug concentration that result from changes in urinary output may be mistakenly interpreted as a new drug use. Normalization f drug excretion to urine creatinine concentration reduces the variability of drug measurement attributable to urine dilution. The time function of creatinine normalized opiate concentration has a log-linear character, and decreases at a rate of 2.5 per day on average. New "normalized" cut-off values were proposed: 225 ng/mg creatinine, 1500 ng/mg creatinine, a d 3750 ng/mg creatinine that corresponds to 300 ng/m/urine, 2000 ng/mL urine, and 5000 ng/mL urine.

Introduction behavior may have taken place under the effects of a psychoactive substance. The basic method used to confirm suspected illegal use of opiates consists in testing these substances in urine (3-6). In the case of detection of opiates, urine is the biological material of choice, as it contains higher substance concentrations than blood, and the collection of samples is non-invasive (7-9). It is accepted that opiates are detectable within three days after the last dose at a cut-off value of300 ng/mL (7,8). Previous studies on estimation ofdetection time, known from literature, involved non-dependent subjects who took a single, low dose (3-12 rag) of heroin administered intravenously, intranasally, intramuscularly, or by inhalation (1,9-12). However, thedoses taken by our patients are several times higher compared to those considered in the mentioned studies. Dosage may alter det ction time (1,9,12-14). Both the route of administration a d continuous use of drug may affect metabolism, as it was shown for morphine (15). In our clinical practice, some patients tested positive for her in even after a week of detoxification. Scarce reports that refer to detection time in dependent subjects have appeared only recently (16,17), and these also report excretion time longer than 3 days.

The aim of this study was to evaluate how long opiates are detectable in urine of dependent subjects who continuously use drugs (Fll.25 according to ICD.10 criteria). We searched for the relation between the time course of opiates excretion and the route of administration, the kind of street heroin ("brown sugar" or "kompot'--homemade poppy straw decoctions) a d the cut-off value.

The demand for assaying psychoactive substances grows continuously. The detection time is the parameter that defines the period of detectability of a substance. The knowledge of etection time is useful in determining the minimum frequency of testing required to find all relapsed cases in therapeutic programs (1,2). It also helps to ascertain whether unlawful "Author to whom correspondence should be addressed. Ewa Taracha, Ph.D., Department of

Neurochemistry, Institute of Psychiatry and Neurology, AI, Sobieskiego 9, 02-957 Warszawa,

Poland. E-mail: taracha@ipin.edu.pl.

Experimental

Subjects

Seventy-one men treated for opiate dependency (Fll.25 according to ICD-10) (18) at the Detoxification Unit of the

Institute of Psychiatry and Neurology in Warsaw ere included in this study. Sixty-nine subjects received methadone during detoxification, and two were treated symptomatically. No

Reproduction (photocopying) of editorial content of this journal is prohibited without publisher's permission. 1 5

Journal of Analytical Toxicology, Vol. 29, January/February 2005 additional opiates, besides methadone, were used during the study. Some of the subjects with severe somatic illnesses were excluded from the study. These were the cases of illnesses requiring intensive treatment (i.e., they were due to potential interaction between the administered rugs and opiate metabolism and excretion) and psychoses. Similarly, the subjects who alternated between different opiates (e.g., heroin or kompot) and/or used different routes of administration (e.g., intravenous and inhalation) during the last 3 months were not taken into account. Patients were kept under continuous observation in hospitalization conditions. Special rocedures were used at Detoxification Ward in order to minimize the possibility of breaking the abstinence. Additionally, the patients were clinically examined several times a day by staff experienced in detecting the symptoms of use of psychoactive substances. The dynamics of abstinence syndrome, measured by the Gossp scale, was periodically assessed. The patients uspected of breaking abstinence were rejected from the study.

The subjects were divided into three drug user groups depending on the type of drug and the route of administration: inhaled heroin, intravenous heroin, or intravenous kompot users.

When inhaling by means of a technique called "chasing the dragon", the heroin is put on a piece of aluminium foil and heated from below with a cigarette lighter. The heroin fumes are then inhaled through a straw. The brown sugar, mainly used for inhalation, is a base of heroin mixed with caffeine and sometimes inert diluents. Intravenous heroin users in the examined group used the brown sugar after dissolving it in citric acid or they injected the kompot. The latter is a homemade poppy straw extract. It is a non-standardized mixture of opium alkaloids and their acetyl derivatives. Main co stituents of the kompot are heroin, 6-acetylmorphine, morphine, and codeine.