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Biomedical subjects

A S Christophersen

Publications and source records attributed to A S Christophersen.

At least 19 recordsLinked to original sources
PubMed2004

Characteristics of drivers testing positive for heroin or ecstasy in Norway.

An increasing number of heroin and ecstasy seizures were recorded by the Norwegian police and customs authorities in the 1990s. The number of apprehended drivers in whom heroin and ecstasy were detected also rose in the same period (Heroin, 1991: n = 17, 1999: n = 320. Ecstasy, 1995: n = 6, 1999: n = 123). Drivers who tested positive for heroin (detected in urine as the metabolite 6-monoacetyl-morphine, 6-MAM) or ecstasy (3,4-methylenedioxy-metamphetamine, MDMA, detected in blood) were characterized with regard to age distribution, drug use pattern, and earlier arrests. In 1998-1999, the police apprehended 9013 drivers on suspicion of being under the influence of drugs other than alcohol. Blood and urine samples from the drivers were sent to the Norwegian Institute of Public Health, Division of Forensic Toxicology and Drug Abuse and analyzed for the most commonly abused drugs. 6-MAM was detected in urine in 7% of the cases (n = 637), representing 542 different drivers (male: 85%, n = 463, female: 15%, n = 79) as some drivers were rearrested several times during the selection period. MDMA was detected in 2% of the cases (n = 190), representing 177 drivers (male: 90%, n = 160, female: 10%, n = 17). The median ages of drivers who tested positive for 6-MAM or MDMA were 32 and 24 years, respectively. Multi-drug use was very common in both groups (83% and 98% for the heroin and ecstasy group, respectively). Drivers in both groups were followed back to 1985 to detect earlier arrests for the same offence. Of the heroin group, 78% (n = 417) had earlier been arrested for drunken or drugged driving. Alcohol was the drug most frequently detected on first arrest. Of the ecstasy group, 47% (n = 83) had earlier been arrested, and amphetamine was most frequently found on first arrest.

Adult↗
PubMed2002

Rearrest rates among Norwegian drugged drivers compared with drunken drivers.

The rearrest rates among Norwegian drugged (n=1102) and a group of drunken drivers (n=850) (BAC: 0.16-0.19%) apprehended during 1992, were 57% (n=629) and 28% (n=238), respectively, when followed prospectively for 7 years. The most important risk factors for recidivism among drugged drivers were previous arrests for drugged or drunken driving (rearrest rate among previous arrests: 73%, no previous arrest: 42%), multi-drug detection at selection (multi-drug: 62%, single drug: 41%), sex (male: 61%, female: 35%) and age (below 36 years: 60%, 36 years and older: 44%). Most of the recidivist drugged drivers were rearrested during the year of selection (21%), followed by 13, 7 and 6%, retrospectively, during the following years. When followed both retrospectively and prospectively for a period extending from 1984 to 1998, 71% (n=779) and 40% (n=344) of the selected drugged and drunken drivers, respectively, were arrested two or more times.

Adolescent↗
PubMed2000

Amphetamine designer drugs - an overview and epidemiology.

The methylenedioxy-derivatives of amphetamine and methamphetamine represent the largest group of designer drugs. The most frequently used compounds are 3,4-methylenedioxy-methamphetamine (MDMA-ecstasy) and 3,4-methylenedioxy-amphetamine (MDA), first synthesised in 1910 (MDA) and 1914 (MDMA), respectively, to be used as an appetite suppressant. At the end of the 1960s, non-medical (recreational) use appeared in the USA, and in the middle of the 1980s in Europe. In Norway, MDMA and related compounds have been detected in forensic samples since the early 1990s. In order to bypass the legal regulations and to produce more potent substances, a number of related compounds have been synthesised, including derivatives with one or more substituents (methoxy, methyl, halogen or sulphur), attached at different positions to the phenylring of amphetamine or methamphetamine. A report from 1998 shows that 0.5-3% of the adult European population, mainly young people, has used ecstasy.

Adolescent↗
PubMed1999

Drugged driving in the Nordic countries--a comparative study between five countries.

The purpose of this study was to compare whether the high incidence of drugged driving in Norway was different to that in the other Nordic countries. All blood samples received by Nordic forensic institutes during one week in 1996, from drivers suspected by the police of driving under the influence (Denmark: n = 255, Finland: n = 270, Iceland: n = 40, Sweden: n = 86, Norway: n = 149), were analysed for alcohol and drugs (benzodiazepines, cannabinoids, amphetamines, cocaine, opiates and a number of antidepressant drugs) independent of the primary suspicion, and using the same analytical cut-off levels at the different institutes. The primary suspicion was directed towards drugs in more than 40% of the Norwegian cases, drugs were detected in more than 70% of these samples. In only 0-3% of the cases from Denmark, Finland and Iceland, were drugs suspected, while the corresponding frequency for Sweden was 17%. However, evidential breath analyses were used for about three-quarters of the Swedish drivers suspected to be influenced by alcohol. Blood alcohol concentrations (BAC's) below the legal limits were found in 32, 18 and 2% of the Norwegian, Icelandic and Finnish cases, respectively (BAC < 0.05%), in 10% of the Danish cases (BAC < 0.08%) and in 20% of the Swedish cases (BAC < 0.02%). Drugs were most frequently found in the Norwegian and Swedish cases with no alcohol (80-83%). Similar frequencies of drugs in samples with BAC's above the legal limits (19-22%), were obtained for all countries. Benzodiazepines, tetrahydrocannabinol and amphetamine represented the most commonly detected drugs. Our results show that differences between Norway and other Nordic countries with regard to drugs and driving, are connected to the selection criteria made by the police and with more focus on drugged driving in Norway.

Adult↗
PubMed1999

[Repeated driving under influence].

Many drivers arrested for driving under the influence have earlier been arrested and convicted for a similar type of violation. The article reviews Norwegian studies on car drivers influenced by alcohol, other drugs than alcohol, and also drivers influenced by amphetamine. The results show that between 10 and 30% of drivers convicted for driving under the influence of alcohol, are rearrested two or more times for the same violation during a subsequent three year period. The recurrence rate is dependent on blood alcohol concentration at the selection time. The recurrence rate among drivers under the influence of drugs other than alcohol is significantly larger (up to 54%), when studied over the same three year period. The number of drivers influenced by amphetamine has increased dramatically during recent years. The recurrence rate among drivers influenced by amphetamine is on part with that of drivers using other drugs than alcohol. There are indications that an increasing number of drunken drivers have changed their abuse pattern during recent years from alcohol to illegal drugs such as amphetamine.

Alcohol Drinking↗
PubMed1998

Study of rearrests for drunken driving in Norway.

The National Institute of Forensic Toxicology (NIFT) in Oslo receives blood samples from all Norwegian drivers suspected of driving under the influence of alcohol. It is well known that a large proportion of the arrested drunken drivers are repeat offenders. The purposes of this investigation was to find the arrest rates (the percentage of subjects arrested once or more) among drunken drivers followed retrospectively and prospectively during the 11-year period 1984-1994 and the probability of 'abstaining' from becoming a recidivist during the 9 years subsequent to the year of selection. By examining the rearrest rates during the 3 following years for drivers selected in 1986, 1989, 1991 and 1992 we tried to look for major effects due to the change in the Norwegian road traffic act of 1988. Altogether 45% of the selected drunken drivers were arrested two or more times. Totally the '9-year survival rate' (i.e. not being rearrested) was 60% for drivers with blood alcohol concentration (BAC) selected from the interval 0.06-0.09%; 56% from BAC 0.13-0.16% and 51% from 0.26-0.29%. The data were further evaluated with respect to frequency of rearrest during 3 years after selection, and was around 30% in 1986, while it was lower for drivers selected in 1992 (19%). An explanation for the reduction in rearrest rate may be the changes in the road traffic act which took place in 1988.

Adolescent↗
PubMed1997

Drugged driving, a review based on the experience in Norway.

Since 1959, the Norwegian Road Traffic Act has prohibited driving under the influence of drugs other than alcohol. On suspicion, the police request a clinical examination from any driver, as well as blood analyses for illegal and prescribed drugs affecting driving performance. During the last few years, there has been a marked increase in the number of drivers suspected of be influenced by drugs (1983, n = 900; 1995, n = 3329). The most commonly detected drugs are tetrahydrocannabinol, amphetamine, benzodiazepines and opiates. Multi-drug use is frequently found (> 60%). The occurrence of amphetamine (1991, n = 216; 1995, n = 937) and heroin (1991, n = 19; 1995, n = 172) has increased considerably. The frequency of drugged drivers apprehended in roadside traffic appears to be at least 10-fold higher in Norway than most other countries. This is probably mainly due to differences between national road traffic acts and the level of attention to the problem, and not to national differences in the prevalence of drugged driving.

Accidents, Traffic↗
PubMed1997

Evidence for CYP2D1-mediated primary and secondary O-dealkylation of ethylmorphine and codeine in rat liver microsomes.

The purpose of the present study was to investigate the role of specific CYPs responsible for the O-dealkylation of ethylmorphine (EM) and codeine (CD) to morphine (M), as well as that of norethylmorphine (NEM) and norcodeine (NCD) to normorphine (NM) in rat liver microsomes. Liver microsomes metabolize EM and CD to M, and NEM and NCD to NM, in the presence of an NADPH-generating system. The metabolites of EM and CD were determined by HPLC with UV and electrochemical detection. In the present study, the role of CYP2D1 in O-dealkylation of EM/NEM and CD/NCD was investigated by use of specific antiCYP antibodies. When testing rabbit antirat CYP2D1, 2E1, 2C11, and 3A2 antibodies, only the antiCYP2D1 antibody inhibited the EM/NEM and CD/NCD O-dealkylase activities significantly. The maximum inhibition achieved was approximately 80% at a protein ratio (IgG to microsomes) of 10:1, p = 0.001. The contribution of CYP2D1 to the O-dealkylation of EM/NEM and CD/NCD was further confirmed by use of the specific CYP2D1 inhibitors quinine and propafenone. Five microM of quinine inhibited the EM/NEM and CD/NCD O-dealkylase activities by approximately 80%. The CYP3A inhibitor troleandomycin (TAO) failed to inhibit the CYP2D1 catalyzed reaction, but did inhibit the N-demethylation of EM and CD. The O-dealkylation of NEM and NCD was also impaired in Dark Agouti rat (DA) liver microsomes. Taken together, the immunoinhibition and chemical-inhibitor studies of rat liver microsomes provided convincing evidence for the involvement of CYP2D1, the rat counterpart of human CYP2D6, in the metabolism of EM/NEM and CD/NCD to the corresponding O-dealkylated metabolites.

Animals↗
PubMed1997

Effects of ethanol on ethylmorphine metabolism in isolated rat hepatocytes: characterization by means of a multicompartmental model.

Hepatic cytochrome P-450 enzymes mediate at least two important biotransformation pathways of codeine and ethylmorphine starting with either N-demethylation or O-dealkylation, producing polar metabolites which are then subsequently glucuronidated. The present study was designed to characterise the acute effects of ethanol on the metabolism of ethylmorphine and to compare it with the effects on codeine in suspensions of freshly isolated rat hepatocytes. Isolated rat hepatocytes from male Wistar rats were prepared by a collagenase perfusion method. Ethylmorphine, codeine and their metabolites were quantified by HPLC with UV detection. The total ethylmorphine elimination rate was reduced by 12% at 5mM and 38% at 100 mM ethanol. The corresponding percentages for codeine were 16 and 43%. In the presence of ethanol the concentrations of several intermediate and end products of ethylmorphine and codeine changed markedly from the control situation. The experimental data were applied to a mathematical compartmental linear model to estimate the influence of ethanol on the separate reaction rates in the two main metabolic pathways. The ratios between reaction rate constants in the ethylmorphine experiments at 100 and 0 mM ethanol were 0.65 for ethylmorphine-->norethylmorphine, 0.63 for norethylmorphine-->normorphine, 0.56 for ethylmorphine-->morphine, 0.49 for morphine-->normorphine, 0.31 for normorphine-->normorphine-3-glucuronide and 0.49 for morphine-->morphine-3-glucuronide. Almost similar effects of ethanol on codeine metabolism were found. In additional experiments, norethylmorphine or norcodeine (50 microM) was incubated with 5 mM to 100 mM of ethanol and the metabolism of both norethylmorphine and norcodeine was found to be inhibited by ethanol in a concentration-dependent manner. The glucuronidation of morphine and normorphine added in separate experiments was also inhibited by ethanol, from 22 to 36% for morphine-3-glucuronide and 30 to 60% for normorphine-3-glucuronide, respectively, in the presence of 5 mM to 100 mM of ethanol. It was concluded that all steps in the metabolism of ethylmorphine (and codeine) leading to the end products morphine-3-glucuronide and normorphine-3-glucuronide were inhibited by ethanol, and that the glucuronidation process were the ones most affected by ethanol.

Animals↗
PubMed1996

Recidivism among drunken and drugged drivers in Norway.

The prevalence of re-arrest among drunken drivers in relation to different blood alcohol concentrations (BAC) at the time of the offences was studied. Between 38 and 50% of arrested drunk drivers were re-arrested for similar offences. The frequency of re-arrests was, however, reduced during 1992 compared with a986, but only significantly for those with a low BAC interval (60-90 mg/d). We conclude that drivers with high re-arrest rates have a careless attitude to the Road Traffic Act and require a different treatment and follow-up programme.

Accidents, Traffic↗
PubMed1995

Female drivers suspected for drunken or drugged driving.

The National Institute of Forensic Toxicology in Oslo receives blood and urine samples from all Norwegian drivers apprehended on suspicion of driving under the influence of alcohol or drugs. In this study, sex differences in use of alcohol and drugs among Norwegian drunken and drugged drivers were presented. In 1992 and 1993, the institute received samples from 11,970 and 5642 suspected drunken and drugged drivers respectively. Women were underrepresented among both suspected drunken (7.6%) and drugged (10.9%) drivers. There were not observed dramatic gender differences in frequency and finding of drugs. The most frequent drugs in addition to alcohol were tetrahydrocannabinol, benzodiazepines and amphetamine. The data suggest that benzodiazepines are found relatively more often in blood from female than from male drugged drivers. Lower proportion of women with blood ethanol concentration over the legal limit was observed.

Adolescent↗
PubMed1995

Automated analysis of free and total concentrations of three antiepileptic drugs in plasma with on-line dialysis and high-performance liquid chromatography.

A fully automated method for determination of the free and total concentration of drugs with a varying degree of protein binding is described. The antiepileptic drugs phenytoin, carbamazepine and phenobarbitone were chosen to demonstrate the utility of this technique. The method was based on the ASTED system and combined on-line equilibrium dialysis at 37 degrees C with concentration of the dialysate on a trace enrichment column and HPLC determination with UV detection. The dialysis cell was a modification of the ASTED dialysis cell and 22% of the free concentration of the drugs were recovered in the recipient channel of the dialyser after 10 min of dialysis at 37 degrees C. The free concentration, the total concentration as well as the drugs protein binding could be determined. The method was shown to be well suited for routine monitoring of the free and the total concentrations of the drugs in plasma from epileptic patients.

Anticonvulsants↗
PubMed1995

Ethylmorphine O-deethylation in isolated rat hepatocytes. Involvement of codeine O-demethylation enzyme systems.

The O-dealkylation of ethylmorphine (EM) and codeine (CD) to morphine (M) co-segregates with debrisoquine/sparteine genetic polymorphism in man. CD O-demethylation is catalysed by cytochrome P450 2D1 (CYP2D1) in rats. In the present study, the O-deethylation of EM was examined and compared with that of CD in suspensions of freshly-isolated hepatocytes prepared by a collagenase method from Wistar rats with and without CYP2D1 inhibitors. Isolated hepatocytes were also prepared from Dark Agouti (DA) rats deficient in CYP2D1, and were incubated with EM or CD. EM, CD and their metabolites were quantified by HPLC with UV detection. EM had a similar pattern of metabolism to that of CD in suspensions of hepatocytes from Wistar rats. Both EM and CD were O-dealkylated to form M plus morphine-3-glucuronide (M3G) and N-demethylated to form norethylmorphine (NEM) or norcodeine (NCD), respectively, which were further metabolized to normorphine (NM) and finally glucuronidated to normorphine-3-glucuronide (NM3G). As compared to hepatocytes from Wistar rats, DA rats were characterized by a markedly decreased formation (70 approximately 75% reduction) of M plus M3G from both EM and CD. Quinine, quinidine, propafenone and sparteine all inhibited EM O-deethylation as well as CD O-demethylation. Quinine was the most potent inhibitor of both these O-dealkylations (Ki = 0.2 microM for both EM and CD, respectively). Quinine as well as the other inhibitors inhibited both EM and CD O-dealkylation competitively and with small differences in Ki versus EM and CD, respectively. The metabolism of EM to M plus M3G and that of CD to M plus M3G was highly correlated when results from the various separate cell suspensions were plotted. In conclusion all findings indicated that the enzyme responsible for O-demethylation of CD, CYP2D1 was also responsible for the O-deethylation of EM to M.

Animals↗
PubMed1995

[Driving under the influence of benzodiazepines. Sale differences in the counties are reflected among drivers suspected of driving under the influence of a drug].

This study was based on all blood samples taken from drivers suspected of being influenced by alcohol and or drugs and sent to the National Institute of Forensic Toxicology in 1992. Benzodiazepines were among the most frequently detected drugs. The ratio between samples containing benzodiazepines and the total number of samples was compared with the sales of benzodiazepines in the different Norwegian provinces. In 95% of the benzodiazepine positive samples, either a combination with other drugs or a concentration significantly higher than usually found after ordinary therapeutic use was observed. These results indicated that the fraction of samples positive on benzodiazepines probably representing drug abuse or misuse correlated with the total prescription of benzodiazepines in the different Norwegian provinces.

Alcohol Drinking↗
PubMed1995

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

1. The pharmacokinetics of ethylmorphine after administration of a single dose of the cough mixture Cosylan were investigated in 10 healthy subjects. 2. The median urinary recovery of ethylmorphine and measured metabolites was 77% over 48 h. The median tmax of unchanged ethylmorphine was 45 min, and the terminal elimination t1/2 was 2 h. Ethylmorphine-6-glucuronide was found to be the major metabolite. 3. Two subjects had significantly lower urinary recovery (0.48 h) of morphine and morphine-glucuronides than the remainder. Furthermore, these two had urinary metabolic ratios (MRO) and partial metabolic clearances (CLmO) for O-deethylation of ethylmorphine tentatively classifying them phenotypically as poor metabolisers of the debrisoquine/sparteine type. 4. Genotyping for cytochrome P450 (CYP) 2D6 alleles revealed five homozygote (wt/wt) and five heterozygote subjects. Two subjects phenotypically classified as poor metabolisers were genotypically CYP2D6A/wt and CYP2D6D/wt, respectively. 5. Serum and urine samples taken more than 8 and 24 h after administration of ethyl-morphine respectively, contained morphine and morphine-glucuronides, but no ethylmorphine, ethylmorphine-6-glucuronide or (serum only) norethylmorphine. Norethylmorphine could be detected after hydrolysis of urine samples in all subjects. The urinary recovery of the active metabolites morphine and morphine-6-glucuronide after administration of ethylmorphine varied by a factor of 9 between individuals. 6. The wide variation in recovery of morphine and morphine-glucuronides after oral administration of ethylmorphine could not be explained simply by a difference in CYP2D6 genotype. Constitutional variation in other enzymatic pathways involved in ethylmorphine metabolism is probably crucial. Ratios of morphine to parent drug cannot be used to distinguish the source of morphine after administration of ethylmorphine. Norethylmorphine should be included in urine assays for opiates in forensic toxicology, and no firm conclusions about the source of morphine are possible based on serum samples obtained more than 24 h after drug administration.

Adult↗