BACKGROUND: A new design of a flow-through coaxial electromembrane extraction (EME) probe that can be on-line coupled with CE instrument is described and tested. The supporting base of the probe is a PDMS microchip with T-shaped channels into which two coaxially arranged capillaries for inlet and outlet solutions are inserted. The extraction part of the probe is a porous polypropylene hollow fiber, sealed at one end and modified with nitrophenyloctyl ether (NPOE) extraction fluid. The internal volume of the extraction probe is 1.1 μL. RESULTS: The EME probe was tested on laboratory samples and methadone was extracted into 3.0 M AcOH as acceptor. The concentration dependence was linear in the range of 0.1-1.0 μg mL-1 at EME 300 s/150 V and in the range of 0.5-10.0 μg mL-1 at EME 100 s/150 V. The enrichment factor was greater than 30 and the LOD was 0.21 μg mL-1. The EME of methadone in clinical samples showed a linear concentration dependence in human urine and a nonlinear concentration dependence in serum. The distribution of methadone in each phase of the extraction system and the effect of extraction membrane thickness on the enrichment factor were studied. The EME probe can be applied repeatedly. SIGNIFICANCE: The supporting base of EME probe and flow gating interface (FGI) are realized by a microfluidic PDMS microchips cast in the laboratory without the use of lithography. A supporting PDMS chip with coaxially arranged capillaries and extraction membrane forms a compact analytical instrument. The entire EME/CE analysis process is performed on a laboratory-made instrument and automated by LabView.

• Klíčová slova
• Capillary electrophoresis, Electromembrane extraction, Flow gating interface, Methadone, On-line coupling,
• MeSH
• elektroforéza kapilární * metody   MeSH
• lidé MeSH
• membrány umělé MeSH
• methadon * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• membrány umělé MeSH
• methadon * MeSH

The circadian clock is one of the most important homeostatic systems regulating the majority of physiological functions. Its proper development contributes significantly to the maintenance of health in adulthood. Methadone is recommended for the treatment of opioid use disorders during pregnancy, increasing the number of children prenatally exposed to long-acting opioids. Although early-life opioid exposure has been studied for a number of behavioral and physiological changes observed later in life, information on the relationship between the effects of methadone exposure and circadian system development is lacking. Using a rat model, we investigated the effects of prenatal and early postnatal methadone administration on the maturation of the circadian clockwork in the suprachiasmatic nucleus (SCN) and liver, the rhythm of aralkylamine N-acetyltransferase (AA-NAT) activity in the pineal gland, and gene expression in the livers of 20-day-old rats. Our data show that repeated administration of methadone to pregnant and lactating mothers has significant effect on rhythmic gene expression in the SCN and livers and on the rhythm of AA-NAT in the offspring. Similar to previous studies with morphine, the rhythm amplitudes of the clock genes in the SCN and liver were unchanged or enhanced. However, six of seven specific genes in the liver showed significant downregulation of their expression, compared to the controls in at least one experimental group. Importantly, the amplitude of the AA-NAT rhythm was significantly reduced in all methadone-treated groups. As there is a strong correlation with melatonin levels, this result could be of importance for clinical practice.

• Klíčová slova
• circadian clock, development, liver, methadone, pineal gland,
• MeSH
• cirkadiánní rytmus fyziologie   MeSH
• epifýza mozková * metabolismus   MeSH
• krysa rodu Rattus MeSH
• laktace MeSH
• melatonin * farmakologie   MeSH
• methadon metabolismus   farmakologie   MeSH
• nucleus suprachiasmaticus fyziologie   MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• melatonin * MeSH
• methadon MeSH

BACKGROUND: Opioid maintenance treatment (OMT) has the potential to reduce mortality rates substantially. We aimed to compare all-cause and overdose mortality among OMT patients while in or out of OMT in two different countries with different approaches to OMT. METHODS: Two nation-wide, registry-based cohorts were linked by using similar analytical strategies. These included 3,637 male and 1,580 female patients enrolled in OMT in Czechia (years 2000-2019), and 6,387 male and 2,078 female patients enrolled in OMT in Denmark (years 2007-2018). The direct standardization method using the European (EU-27 plus EFTA 2011-2030) Standard was employed to calculate age-standardized rate to weight for age. All-cause and overdose crude mortality rates (CMR) as number of deaths per 1,000 person years (PY) in and out of OMT were calculated for all patients. CMRs were stratified by sex and OMT medication modality (methadone, buprenorphine, and buprenorphine with naloxone). RESULTS: Age-standardized rate for OMT patients in Czechia and Denmark was 9.7/1,000 PY and 29.8/1,000 PY, respectively. In Czechia, the all-cause CMR was 4.3/1,000 PY in treatment and 10.8/1,000 PY out of treatment. The overdose CMR was 0.5/1,000 PY in treatment and 1.2/1,000 PY out of treatment. In Denmark, the all-cause CMR was 26.6/1,000 PY in treatment and 28.2/1,000 PY out of treatment and the overdose CMR was 7.3/1,000 PY in treatment and 7.0/1,000 PY out of treatment. CONCLUSION: Country-specific differences in mortality while in and out of OMT in Czechia and Denmark may be partly explained by different patient characteristics and treatment systems in the two countries. The findings contribute to the public health debate about OMT management and may be of interest to practitioners, policy and decision makers when balancing the safety and accessibility of OMT.

• Klíčová slova
• buprenorphine, buprenorphine with naloxone, methadone, mortality, opioid agonist treatment, opioid maintenance treatment, registry-based study, treatment outcomes,
• MeSH
• buprenorfin * terapeutické užití   MeSH
• lidé MeSH
• methadon škodlivé účinky   MeSH
• opiátová substituční terapie škodlivé účinky   metody   MeSH
• poruchy spojené s užíváním opiátů * farmakoterapie   MeSH
• předávkování léky * epidemiologie   farmakoterapie   etiologie   MeSH
• registrace MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• buprenorfin * MeSH
• methadon MeSH

The presence of pharmaceuticals (PHA) and narcotics (NAR) in wastewater (WW) has attracting growing interest due to concern for aquatic environment and the possibility to exploit their presence to estimate drug consumption by population. This work aims to (i) quantify PHA and NAR in the WW of the Brno metropolitan area, (ii) determine the effectiveness of the current conventional wastewater treatment plant (WWTP), and (iii) estimate the illicit drug (ID) consumption. 23 PHA and 9 NAR were frequently detected in the untreated WW and studied for their removal. One year monitoring was carried out to highlight a possible seasonal pattern with PHA and NAR load in WW, WWTP effectiveness, and illicit consumption. Results highlighted that the most abundant PHA and NAR were caffeine (73.9 ± 6.9 μg L-1) and methamphetamine (2.3 ± 0.1 μg L-1) while oxazepam (0.13 ± 0.05 μg L-1) and EDDP (0.02 ± 0.01 μg L-1) were the lowest ones, respectively. Only paracetamol, caffeine, atenolol, ciprofloxacin, amphetamine, cocaine, morphine, and benzoylecgonine exhibited a high biodegradability being removed almost completely (> 90 %). A predominant illicit use of methamphetamine was estimated (17 ± 0.6 doses 1000.inh-1 d-1) that might suggest a higher number of consumers than previous official estimation. A lower abuse of cocaine (2.7 ± 0.5 doses 1000.inh-1 d-1), amphetamine (2.2 ± 0.3 doses 1000.inh-1 d-1), methadone (1.1 ± 0.2 doses 1000.inh-1 d-1), heroin (0.9 ± 0.2 doses 1000.inh-1 d-1), and MDMA (0.7 ± 0.1 doses 1000.inh-1 d-1) was found. A seasonality pattern was highlighted for some PHA and NAR influent load and removal, and, about ID consumption, only for heroin and methadone. These results will be useful for water utilities, to enhance the knowledge about the presence and removal of PHA and NAR, and local and national authorities to evaluate and counteract the problem of ID abuse.

• Klíčová slova
• Emerging contaminants, Environmental surveillance, Pervitine, Pharmaceutical compounds removal, Public health, WBE,
• MeSH
• amfetamin MeSH
• chemické látky znečišťující vodu * analýza   MeSH
• epidemiologie odpadních vod MeSH
• heroin MeSH
• kofein MeSH
• kokain * analýza   MeSH
• lidé MeSH
• methadon MeSH
• methamfetamin * MeSH
• monitorování životního prostředí MeSH
• narkotika MeSH
• odhalování abúzu drog metody   MeSH
• odpadní voda MeSH
• poruchy spojené s užíváním psychoaktivních látek * epidemiologie   MeSH
• roční období MeSH
• zakázané drogy * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amfetamin MeSH
• chemické látky znečišťující vodu * MeSH
• heroin MeSH
• kofein MeSH
• kokain * MeSH
• methadon MeSH
• methamfetamin * MeSH
• narkotika MeSH
• odpadní voda MeSH
• zakázané drogy * MeSH

Intraocular pressure (IOP), pupil size (PS), and tear production are variables important in maintaining eye homeostasis. The purpose of this study was to determine the effects of methadone on IOP, PS, and tear production measured by Schirmer I tear test (STT-I) in healthy nonpainful dogs. A prospective, randomized, "double-blind" clinical study was performed. A total of 40 healthy conscious client-owned dogs were included in the study. Dogs were allocated randomly to 1 of 3 groups and given intravenous methadone 0.3 mg/kg (Met-IV, n = 15), intramuscular methadone 0.3 mg/kg (Met-IM, n = 15), or saline 0.3 mL/kg (SAL, n = 10). IOP, PS, STT-I, heart rate (HR), and mean arterial pressure (MAP) were measured prior to (baseline) and at 2, 5, 10, 20, and 30 minutes after drug administration. Data were analyzed using 1-way and 2-way repeated measures ANOVA or their nonparametric equivalents (P < .05). No significant differences in IOP and PS within or between the groups were detected. In the Met-IV group, the STT-I decreased significantly after 30 minutes (P = .025), however, the values remained within the physiological ranges. In Met-IV group, HR decreased significantly at 5, 10, 20, and 30 minutes, respectively. No other significant differences were observed. Methadone administered at a dose of 0.3 mg/kg intravenously or intramuscularly seems to cause within 30 minutes no clinically important effect on IOP, PS, and STT-I in healthy conscious nonpainful dogs without ocular abnormalities.

• Klíčová slova
• Schirmer tear test, analgesic, canine, eye, tonometry,
• MeSH
• methadon farmakologie   MeSH
• nemoci psů * MeSH
• nitrooční tlak MeSH
• oční nemoci * veterinární   MeSH
• prospektivní studie MeSH
• psi MeSH
• pupila MeSH
• tonometrie oční MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie veterinární MeSH
• Názvy látek
• methadon MeSH

OBJECTIVES: Long-term monitoring of the mutual effects of chronic viral hepatitis C (VHC) treatment and tailored addiction treatment. In 2016, the World Health Organization (WHO) published an action plan to eliminate viral hepatitis C globally by 2030. People who inject drugs (PWID) are a key population that needs increased attention and care. Two decades before the announcement of the WHO plan for the global elimination of HCV (hepatitis C virus), the Remedis Medical Facility, where the study was conducted, established a “Comprehensive Care Program for patients with substance use disorders and addictive behaviour”. METHODS: We evaluated all patients who were in the methadone program as of 1 March 2020, regardless of OST duration, OST dosage, age or gender. Their epidemiological and demographic data obtained during a structured clinical interview and laboratory test results were analysed. RESULTS: Of 24 patients on methadone substitution therapy, 12 (50%) were anti-HCV negative before starting OST. None of them became newly infected with hepatitis C virus (HCV) during OST. The remaining 12 of the study patients were anti-HCV positive. Ten of them have already undergone successful treatment for viral hepatitis. Two patients were re-infected with HCV. CONCLUSION: The presented work confirms the high efficacy of chronic VHC treatment among PWID in inducing suitable conditions. We consider combination of HCV infection treatment and targeted tailored addiction treatment as a starting point for achieving control over the HCV epidemic in the Czech Republic, with a possible positive impact on other blood-borne infections related to risky behaviour.

• Klíčová slova
• HCV (hepatitis C virus), MTD (methadone), OST (opioid substitution treatment), PWID (People Who Injected Drugs), Remedis, Prague, VHC (viral hepatitis C),
• MeSH
• antivirové látky terapeutické užití   MeSH
• hepatitida C * farmakoterapie   epidemiologie   MeSH
• intravenózní abúzus drog * komplikace   epidemiologie   MeSH
• léčivé přípravky * MeSH
• lidé MeSH
• methadon terapeutické užití   MeSH
• opiátová substituční terapie MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antivirové látky MeSH
• léčivé přípravky * MeSH
• methadon MeSH

There is lack of knowledge about the safety of treatment with methadone and buprenorphine as part of opioid maintenance treatment (OMT) during pregnancy. The purpose of this study was to examine neonatal outcomes concerning the use of OMT during pregnancy. We used nationwide registry linkages from the Czech Republic (2000-2014) and Norway (2004-2013). We compared prenatally OMT-exposed newborns with (a) newborns of women hospitalized with opioid use disorder during pregnancy in the Czech sample and (b) newborns with neonatal abstinence syndrome (NAS) in Norway. We performed multivariate linear and binary logistic regression exploring the associations between OMT and neonatal outcomes (growth parameters, gestational age, fetal death, small for gestational age, Apgar score, and NAS). Regression coefficients (b) and odds ratios (ORs) were estimated. The cohorts consisted of 333 Czech, and 235 Norwegian OMT-exposed newborns, and 106 and 294 newborns in the comparison groups, respectively. In both countries, the neonatal growth parameters were similar in the OMT and the comparison groups. In Norway, OMT exposure prolonged gestational age (adjusted b = 0.96 weeks, 95% confidence interval [CI] =0.39-1.53) while the odds of preterm birth and Apgar score at 5 minutes were lower than in the comparison group (adjusted OR = 0.35, 0.16-0.75 and aOR = 0.21, 0.06-0.78, respectively). Newborns of women in OMT had similar growth parameters as newborns of women with opioid use disorders who were not in OMT during pregnancy. Overall, our findings do not suggest that OMT results in worse neonatal outcomes.

• Klíčová slova
• buprenorphine, methadone, neonate, opioid maintenance treatment, prenatal exposure,
• MeSH
• buprenorfin terapeutické užití   MeSH
• dospělí MeSH
• komplikace těhotenství farmakoterapie   MeSH
• lidé MeSH
• logistické modely MeSH
• methadon terapeutické užití   MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• novorozenecký abstinenční syndrom epidemiologie   MeSH
• opiátová substituční terapie MeSH
• poruchy spojené s užíváním opiátů farmakoterapie   MeSH
• registrace MeSH
• těhotenství MeSH
• vývoj dítěte MeSH
• zpožděný efekt prenatální expozice epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Norsko epidemiologie   MeSH
• Názvy látek
• buprenorfin MeSH
• methadon MeSH

BACKGROUND AND AIMS: Our understanding of the long-term safety of prenatal exposure to opioid maintenance treatment (OMT) is insufficient. We compared childhood morbidity (0-3 years) between OMT-exposed and relevant comparison groups. DESIGN: Nation-wide, registry-based cohort study. Registries on reproductive health, addiction treatment, hospitalization and death were linked using identification numbers. SETTING: The Czech Republic (2000-14). PARTICIPANTS: Children with different prenatal exposure: (i) mother in OMT during pregnancy (OMT; n = 218), (ii) mother discontinued OMT before pregnancy (OMT-D; n = 55), (iii) mother with opioid use disorder, but not in OMT during pregnancy (OUD; n = 85) and (iv) mother in the general population (GP) (n = 1 238 452) MEASUREMENTS: Episodes of hospitalization were observed as outcomes. Information on in-patient contacts, length of stay and diagnoses (International Classification of Diseases version 10) were assessed. Binary logistic regressions were conducted to estimate the associations between OMT exposure and the outcomes, crude and adjusted for the socio-economic status and smoking. FINDINGS: No significant differences were found in the overall proportion of hospitalization among OMT-exposed children, children of OMT-D and children of women with OUD [54.1%, 95% confidence interval (CI) = 47.3-60.1%; 47.3%, 95% CI = 33.9-61.1%; 51.8%, 95% CI = 40.7%-62.6%], while the proportion was significantly lower (35.8%, 95% CI = 35.7-35.8%) in the GP. There were no significant differences in risk of specific diagnoses between OMT-exposed children, children of OMT-D and children of women with OUD. In the adjusted analyses, differences between OMT-exposed and children in the GP were still present for infections and parasitic diseases (OR = 2.0, 95% CI = 1.4-2.7), diseases of the digestive system (OR = 1.7, 95% CI = 1.2-2.6) and diseases of the skin and subcutaneous tissue (OR = 1.9, 95% CI = 1.2-3.2). CONCLUSION: This study did not find clear evidence for an increase in risk of morbidity during the first 3 years of life in children with prenatal opioid maintenance treatment exposure compared with children of women who discontinued such treatment before pregnancy or suffered from opioid use disorder without this treatment. Compared the general population, there appears to be an increased risk of hospitalizations for infectious, gastrointestinal and skin diseases.

• Klíčová slova
• Buprenorphine, child morbidity, health registries, hospitalization, long-term effects, methadone, opioid maintenance treatment, prenatal exposure,
• MeSH
• buprenorfin terapeutické užití   MeSH
• délka pobytu statistika a číselné údaje   MeSH
• dospělí MeSH
• hospitalizace statistika a číselné údaje   MeSH
• infekce epidemiologie   MeSH
• kojenec MeSH
• komplikace těhotenství farmakoterapie   epidemiologie   MeSH
• kožní nemoci epidemiologie   MeSH
• lidé MeSH
• methadon terapeutické užití   MeSH
• mladý dospělý MeSH
• nemoci trávicího systému epidemiologie   MeSH
• novorozenec MeSH
• opiátová substituční terapie statistika a číselné údaje   MeSH
• opioidní analgetika terapeutické užití   MeSH
• poruchy spojené s užíváním opiátů farmakoterapie   epidemiologie   MeSH
• předškolní dítě MeSH
• registrace MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• buprenorfin MeSH
• methadon MeSH
• opioidní analgetika MeSH

Chiral ITP of the weak base methadone using inverse cationic configurations with H+ as leading component and multiple isomer sulfated β-CD (S-β-CD) as leading electrolyte (LE) additive, has been studied utilizing dynamic computer simulation, a calculation model based on steady-state values of the ITP zones, and capillary ITP. By varying the amount of acidic S-β-CD in the LE composed of 3-morpholino-2-hydroxypropanesulfonic acid and the chiral selector, and employing glycylglycine as terminating electrolyte (TE), inverse cationic ITP provides systems in which either both enantiomers, only the enantiomer with weaker complexation, or none of the two enantiomers form cationic ITP zones. For the configuration studied, the data reveal that only S-methadone migrates isotachophoretically when the S-β-CD concentration in the LE is between about 0.484 and 1.113 mM. Under these conditions, R-methadone migrates zone electrophoretically in the TE. An S-β-CD concentration between about 0.070 and 0.484 mM results in both S- and R-methadone forming ITP zones. With >1.113 mM and < about 0.050 mM of S-β-CD in the LE both enantiomers are migrating within the TE and LE, respectively. Chiral inverse cationic ITP with acidic S-β-CD in the LE is demonstrated to permit selective ITP trapping and concentration of the less interacting enantiomer of a weak base.

• Klíčová slova
• Capillary electrophoresis, Chiral separation, Computer simulation, Isotachophoresis, Sulfated cyclodextrin,
• MeSH
• beta-cyklodextriny chemie   MeSH
• inosintrifosfát chemie   MeSH
• izotachoforéza metody   MeSH
• kationty MeSH
• methadon * chemie   izolace a purifikace   MeSH
• počítačová simulace MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• inosintrifosfát MeSH
• kationty MeSH
• methadon * MeSH

Opioid agonist therapy (OAT) has been available in a standard regime in the Czech Republic since 2000. Buprenorphine is the leading medication, while methadone is available only in a few specialised centres. There is an important leakage of buprenorphine onto the illicit market, and the majority of Czech opioid users are characterised by the misuse (and injecting) of diverted buprenorphine medications. Most prescribed buprenorphine for OAT is not covered by current national health insurance schemes, and patients have to pay considerable prices to afford their treatment. This affordability barrier together with limited accessibility is likely the leading factor of limited coverage of OAT and of recent stagnation in the number of patients in the official treatment programmes in the Czech Republic. It also encourages doctor shopping and the re-selling of parts of their medication at a higher price, which represents the main factor that drives the Czech illicit market for buprenorphine, but at the same time co-finances the medication of clients in official OAT programmes. Improving access to OAT by making it financially affordable is essential to further increase OAT coverage and is one of the factors that can reduce the illicit market with OAT medications.

• Klíčová slova
• Access, Availability, Barriers, Buprenorphine, Cost, Crime, Diversion, Heroin, Illicit market, Mortality, Opioid substitution treatment, Opioids,
• MeSH
• buprenorfin * MeSH
• dospělí MeSH
• dostupnost zdravotnických služeb statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methadon terapeutické užití   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• narkotika terapeutické užití   MeSH
• opiátová substituční terapie statistika a číselné údaje   MeSH
• opioidní analgetika * MeSH
• poruchy spojené s užíváním opiátů epidemiologie   rehabilitace   MeSH
• poruchy spojené s užíváním psychoaktivních látek epidemiologie   MeSH
• zakázané drogy MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• buprenorfin * MeSH
• methadon MeSH
• narkotika MeSH
• opioidní analgetika * MeSH
• zakázané drogy MeSH