Pregabalin Abuse amongst Opioid Substitution Treatment Patients.

Pregabalin (Lyrica®) is used in treating epilepsy, nerve pain and anxiety. Pregabalin was initially thought to have a low misuse potential however there are emerging reports of Pregabalin being abused. A study was commenced at the National Drug Treatment Centre's (NDTC) Drug Analysis Laboratory to determine the level of usage of Pregabalin within the addiction services population in Ireland. A total of 498 urine samples representing samples from 440 individual opioid substitution patients, initially screened by immunoassay for drugs of abuse, were subjected to further analysis for Pregabalin by Liquid Chromatography/Mass Spectrometry (LC/MS). Of 440 patients tested, 39 tested positive for Pregabalin (9.2%). Only 10 patients from this group were prescribed this drug to our knowledge thus giving an estimated rate of misuse of 7.0%. Other drugs detected in the Pregabalin positive patients were Opiates (31.8%), Cocaine (11.4%), Benzodiazepines (79.5%) and Cannabis (77.8%). Our study confirms that Pregabalin abuse is taking place amongst the addiction services population. We believe that misuse of this prescription drug is a serious emerging issue which should be monitored carefully.

Excretion of afobazole and its metabolites with urine and feces in rats.

The amount of afobazole and identified metabolites was measured in the urine and feces of rats after intraperitoneal and peroral administration of the drug in a dose of 25 mg/kg. Over 1 day after intraperitoneal or peroral treatment with afobazole, urine and feces contained 0.1% initial compound (from administered dose) and 42.1% metabolites.

Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro.

Reported adverse drug interactions with the popular herb kava have spurred investigation of the mechanisms by which kava could mediate these effects. In vivo and in vitro experiments were conducted to examine the effects of kava extract and individual kavalactones on cytochrome P450 (P450) and P-glycoprotein activity. The oral pharmacokinetics of the kavalactone, kawain (100 mg/kg), were determined in rats with and without coadministration of kava extract (256 mg/kg) to study the effect of the extract on drug disposition. Kawain was well absorbed, with >90% of the dose eliminated within 72 h, chiefly in urine. Compared with kawain alone, coadministration with kava extract caused a tripling of kawain AUC(0-8 h) and a doubling of C(max). However, a 7-day pretreatment with kava extract (256 mg /kg/day) had no effect on the pharmacokinetics of kawain administered on day 8. The 7-day pretreatment with kava extract only modestly induced hepatic P450 activities. The human hepatic microsomal P450s most strongly inhibited by kava extract (CYP2C9, CYP2C19, CYP2D6, CYP3A4) were inhibited to the same degree by a "composite" kava formulation composed of the six major kavalactones contained in the extract. K(i) values for the inhibition of CYP2C9 and CYP2C19 activities by methysticin, dihydromethysticin, and desmethoxyyangonin ranged from 5 to 10 microM. Kava extract and kavalactones (< or =9 microM) modestly stimulated P-glycoprotein ATPase activities. Taken together, the data indicate that kava can cause adverse drug reactions via inhibition of drug metabolism.

Concurrent substance use and outcome in combined behavioral and naltrexone therapy for opiate dependence.

UNLABELLED: The effect of concurrent nonopiate drug use on outcome of treatment for opiate dependence. METHOD: Forty-seven opiate-dependent patients received a 6-month course of outpatient treatment with naltrexone and cognitive-behavioral therapy (behavioral naltrexone therapy, BNT) at a university-based research clinic. Opiate-negative urines and naltrexone ingestion were rewarded with monetary vouchers. Abstinence from other drugs was encouraged verbally, but no contingencies were placed on nonopiate drug use. The proportions of all urines (collected twice weekly) positive for cocaine, cannabis, and benzodiazepines over the course of treatment were evaluated as predictors of outcome of opiate dependence treatment, as measured by proportion of opiate-positive urines, days retained in treatment, and proportion of naltrexone doses taken, using Pearson product moment correlations and one-way analysis of variance (ANOVA). RESULTS: The majority of patients (78%) used a nonopiate drug at least once during the trial. There were no significant correlations between concurrent drug use measures and opiate dependence treatment outcomes, indicating no simple linear relationship between these measures. However, when concurrent drug use was trichotomized into abstinent, intermittent, and heavy use groups, groups with intermittent use had superior outcome compared to both abstinent and heavy use groups in several contrasts. CONCLUSIONS: Intermittent use of nonopiate drugs is common during outpatient treatment for opiate dependence and may be a favorable prognostic indicator. This may support a "harm reduction" approach as opposed to a strict abstinence-oriented approach. Further research is needed to identify the optimal therapeutic stance toward other drug use during treatment for opiate dependence.

[The determination of lorazepam in human urine by gas chromatography/nitrogen-phosphorus detector].

A method to assay lorazepam in human urine has been developed. After addition of hydroxyethylflurazepam (internal standard) and hydrolysis with beta-glucuronidase, the lorazepam and hydroxyethylflurazepam were extracted with ethyl ether at pH 10.8. The analysis was performed on an HP-5 capillary column with nitrogen-phosphorus detector(NPD). The detection limit and recovery of analytes in urine were 5 micrograms/L and (83.4 +/- 3.1)% respectively. The method was successfully applied to urine specimens collected from healthy human volunteers who have ingested 2 mg of lorazepam. The method was sensitive enough to assay urine specimen excreted at 32 h after taking the medicine by volunteers.

A review of patients on methadone maintenance.

This study involves a review of 178 patients on a strictly monitored methadone maintenance programme. All patients had a minimum of 9 years of intravenous drug misuse. 35.7% were HIV positive, 55.7% males and 29% females had previous prison sentences. On average patients had undergone 3.26 out-patient and 0.9 in-patient detoxification. 46.1% had attempted rehabilitation in the past. Out of 25,470 urine samples obtained while on the programme, 10.8% were positive for opiates, 19.2% for benzodiazepines, 32.5% for cannabis, 4.92% for alcohol and 2.27% for amphetamines. Long history of misuse, multiple custodial sentences, previous unsuccessful rehabilitation and positive HIV status were associated with acceptance for maintenance. Frequency of urinalysis, and results triggering dose change can effectively reduce illicit drug use.