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Biomedical subjects

Eric T Moolchan

Publications and source records attributed to Eric T Moolchan.

At least 55 records · Page 3Linked to original sources

Clove cigarette smoking: biochemical, physiological, and subjective effects.

Alternative tobacco products such as clove (kreteks) and bidi cigarettes have become increasingly popular among US smokers. The nicotine content of a popular clove cigarette (Djarum Special) filler averaged 7.4 mg; conventional cigarettes contained 13.0 mg. However, smoke yields from standardized machine-smoking analysis indicated it delivered more nicotine, carbon monoxide (CO), and tar than conventional cigarettes. In a clinical study, nicotine delivery, physiologic, and subjective effects of the clove cigarette were compared to their own brand of cigarette in 10 adult smokers (7 males). Average time to smoke the clove cigarette (549 s) and number of puffs (15.1) were significantly greater than own brand (314 s and 9.4 puffs). Increases in venous plasma nicotine and exhaled CO after smoking the clove cigarette (17.4 ng/ml; 6 ppm) were similar to those after own brand (17.6 ng/ml; 4.5 ppm). Maximal changes in heart rate (HR), systolic, and diastolic blood pressures (BP) did not differ significantly between the clove and own brand of cigarette. Compared to their own brand of cigarette, the clove cigarette was rated as better tasting and being distinctly different. Our findings indicate that clove cigarettes deliver significant quantities of nicotine, CO, and presumably other toxic components of tobacco smoke. Taste satisfaction, aromatic odor, and novelty may contribute to their appeal to young smokers.

Adult↗

EEG effects of conventional and denicotinized cigarettes in a spaced smoking paradigm.

Although there is a documented association between plasma nicotine levels and smoking behavior, recent studies indicate that denicotinized cigarettes reduced craving and symptoms of tobacco withdrawal. Denicotinized cigarettes (that deliver tar but insignificant amounts of nicotine) and conventional cigarettes were compared in a within-subject spaced smoking study. In six sessions, subjects (n=10) smoked denicotinized cigarettes or conventional cigarettes every 30, 60 or 240 min (8, 4 or 1 cigarette(s)). EEG effects of the last cigarette of each session were deduced by comparisons with EEG recordings collected before smoking. Conventional cigarettes increased spectral edge EEG frequency, decreased theta power and increased beta1 power. Denicotinized cigarettes decreased spectral frequency. The EEG effects of both cigarettes depended upon the recentness of smoking. The results indicate that nicotine delivery, recentness and the process of smoking importantly influence the EEG; other, non-nicotine components of tobacco smoke may also exert EEG effects.

Adult↗

A factor analysis of the Fagerström Test for Nicotine Dependence (FTND).

Psychometric study of the Fagerström Test for Nicotine Dependence (FTND) provides insight into its structure and the dimensions of nicotine addiction it assesses. We evaluated the factor structure of the FTND in 541 research volunteers, most with histories of polysubstance use. Tetrachoric and phi correlation techniques were utilized and promax- and varimax-rotated solutions are reported. Two factors were found. Factor 1 was defined by questions regarding time to first cigarette in after waking, which cigarette is most preferred, and prominence of morning smoking. Factor 2 was defined by questions regarding difficulty refraining from smoking, amount smoked, and smoking while ill. The question "How soon on waking do you smoke your first cigarette?" loaded substantially on both Factor 2 and Factor 1. Repeating the analyses after stratification by gender did not change the results. The factor structure from our sample population was similar to results reported by previous studies with different types of populations. We propose that Factor 1 assesses the degree of urgency to restore nicotine levels to a given threshold after nighttime abstinence, whereas Factor 2 reflects the persistence with which nicotine levels are maintained at about that threshold during waking hours. Thus, the FTND may assess distinguishable self-reportable pharmacological dimensions of nicotine addiction. These two dimensions may provide indirect assessment of a smoker's daily nicotine intake. Testing this hypothesis requires correlation of biomarkers and responses to specific items of the FTND.

Adolescent↗

Youth tobacco control research and activities in the United States: the current national landscape.

This paper highlights the increasing level of collaboration, resource sharing, and consensus building in youth tobacco control taking place in the United States. Better knowledge of current research, activities, and collaborations in this area will help in the planning of activities and the rational allocation of funds for tobacco control programs, research, advocacy, and the counter-advertising activities. We defined three general classifications for organizations that had national youth tobacco control activities: Government centers and institutes, government organizations, and bridging organizations. We asked national experts in our own organization and all other included organizations to suggest additional groups for inclusion. After gathering available public information on each organization from Web sites and printed materials, we than solicited additional information by personal communication with individuals in leadership positions for youth tobacco control within each group. We developed a uniform framework to present a clear picture of each group in the areas of institutional conception, general goals, youth tobacco control research, and youth tobacco control activities. The tables provide a helpful reference guide presenting the institutional conception, goals, funding for research, activities, and Web sites for the institutions and organizations discussed here. Many groups have current youth tobacco control priorities in the United States. This synthesis of current research, funding sources, programmatic activities, and collaborations in the United States will be a valuable resource for clinicians, tobacco control advocates, researchers, and program planners.

Adolescent↗

Smoking topography: reliability and validity in dependent smokers.

Data from two studies were analyzed to determine whether smoking through the mouthpiece of a topography unit yields consistent measures over time and to verify that smoking through a mouthpiece results in a similar degree of smoke exposure as conventional smoking. In both studies, subjects smoked their usual brand of cigarette ad libitum. In study A, subjects (n=7) smoked through a mouthpiece on 4 separate experimental days. In study B, subjects (n=10) smoked on 2 separate days: Once conventionally and once through a mouthpiece. In both studies, exhaled carbon monoxide (CO) and physiological effects (heart rate and blood pressure) were measured before and after smoking. In study B, plasma nicotine concentrations also were measured. In study A, puff volume, puff duration, interpuff interval, and maximum puff velocity averaged 30.8 ml,.9 s, 19.9 s, and 44.6 ml/s, respectively. Intraclass correlation coefficients computed for puff volume (0.66), puff duration (0.75), and maximum puff velocity (0.68) indicated that these measures showed good reliability. In study B, smoking through the mouthpiece yielded similar topographical (time to smoke and number of puffs per cigarette) measures as conventional smoking. Also similar were changes in biochemical values: Plasma nicotine (18.5 ng/ml vs. 25.5 ng/ml), exhaled CO (4.6 ppm vs. 5.1 ppm), and heart rate (8.6 beats/min vs. 7.4 beats/min) for conventional and topography mouthpiece smoking conditions, respectively. Topography measures did not differ significantly between the two studies. Overall, the data from these two small-sample studies suggest that smoking topography provides a valid and reliable index of conventional smoking and an indirect measure of smoke exposure.

Adult↗

Tobacco Craving Questionnaire: reliability and validity of a new multifactorial instrument.

This study documented the initial reliability and validity of the Tobacco Craving Questionnaire (TCQ), a new multidimensional questionnaire to assess tobacco craving. Current cigarette smokers (n=213) not attempting to reduce or quit smoking completed the 47-item TCQ and other forms assessing demographics, tobacco and other drug use history, quit attempts, and current mood. Exploratory factor analyses and structural equation modeling indicated that a four-factor solution best described the item structure. Factor subscales derived from the 17 items with significant loadings had low to high internal consistencies and interitem correlations and exhibited low to moderate, positive intercorrelations. Factor scales were significantly correlated with single-item measures of craving, current mood, and daily cigarette smoking. Results indicated that four specific constructs characterized craving for tobacco: (a) Emotionality, or smoking in anticipation of relief from withdrawal symptoms or negative mood, (b) expectancy, or anticipation of positive outcomes from smoking, (c) compulsivity, or an inability to control tobacco use, and (d) purposefulness, or intention and planning to smoke for positive outcomes. These preliminary data suggest that the TCQ is a reliable and valid instrument for assessing tobacco craving in individuals not attempting to reduce or quit smoking.

Adult↗

Health and performance related reasons for wanting to quit: gender differences among teen smokers.

Adolescents frequently state health as a broad-ranging reason for wanting to quit smoking. Much less is known regarding performance-related reasons. We hypothesized that more male than female smokers want to quit for performance-related reasons (e.g., to improve athletic performance). As part of a telephone screen to determine eligibility for participation in a cessation trial in Baltimore, Maryland, 1999-2001, 509 teenage smokers [mean age 15.78 +/- 1.65 years (range 11-21), 60.9% female, 32.6% African-American] were asked the open-ended question: "Why do you want to quit?" Responses were subsequently grouped into categories that included health, performance, cost, social influences, setting an example for others, self-efficacy, cosmetics, no perceived positive reinforcement, or unknown reasons. Health was the most commonly stated primary and overall reason for wanting to quit among both boys and girls. Sixty-five percent of teen smokers endorsing health reasons were girls, and 51% of those endorsing performance-related reasons were boys (chi2(2) = 7.78, p = 0.02). Recognizing the greater concern for performance-related issues among boys is important for designing and engaging young smokers into cessation interventions.

Adolescent↗

Sensitivity, specificity, and efficiency in detecting opiates in oral fluid with the Cozart Opiate Microplate EIA and GC-MS following controlled codeine administration.

Oral fluid specimens (N = 1406) were collected from 19 subjects prior to and up to 72 h following controlled administration of oral codeine. Volunteers provided informed consent to participate in this National Institute on Drug Abuse Institutional Review Board-approved protocol. A modification of Cozart Microplate Opiate EIA Oral Fluid Kit (Opiate ELISA), employing codeine calibrators, was used for semiquantitative analysis of opiates, followed by gas chromatography-mass spectrometry (GC-MS) for the confirmation and quantitation of codeine, norcodeine, morphine, and normorphine in oral fluid. GC-MS limits of detection and quantitation were 2.5 microg/L for all analytes. The Substance Abuse and Mental Health Services Administration (SAMHSA) has proposed a 40-microg/L opiate screening and a 40-microg/L morphine or codeine confirmation cutoff for the detection of opiate use. Oral fluid opiate screening and confirmation cutoffs of 30 micro g/L are in use in the U.K. Utilizing 2.5-, 20-, 30-, and 40-microg/L GC-MS cutoffs, 26%, 20%, 19%, and 18% of the oral fluid specimens were positive for codeine or one of its metabolites. Six Opiate ELISA/confirmation cutoff criteria (2.5/2.5, 10/2.5, 20/20, 30/20, 30/30, and 40/40 microg/L) were evaluated. Calculations for Opiate ELISA sensitivity, specificity, and efficiency were determined from the number of true-positive, true-negative, false-positive, and false-negative results at each screening/confirmation cutoff. Sensitivity, specificity, and efficiency for the lowest cutoff were 91.5%, 88.6%, and 89.3%. Application of the cutoff currently used in the U.K. yielded sensitivity, specificity, and efficiency results of 79.7%, 99.0%, and 95.4% and similar results of 76.7%, 99.1%, and 95.1% when applying the SAMHSA criteria. These data indicate that the Opiate ELISA efficiently detects oral codeine use. In addition, the data, collected following controlled oral codeine administration, may aid in the interpretation of opiate oral fluid test results and in the selection of appropriate oral fluid screening and confirmation cutoffs.

Administration, Oral↗

Cozart RapiScan Oral Fluid Drug Testing System: an evaluation of sensitivity, specificity, and efficiency for cocaine detection compared with ELISA and GC-MS following controlled cocaine administration.

Oral fluid has become a widely accepted alternative matrix for drugs of abuse detection. Immunoassays have been developed for on-site testing of cocaine and metabolites in oral fluid. The performance of the Cozart RapiScan Oral Fluid Drug Testing System (CRS) was evaluated in comparison with Cozart Microplate Enzyme Immunoassay Cocaine Oral Fluid Kit (COC ELISA) and gas chromatography-mass spectrometry (GC-MS) at several screening and confirmation cutoffs, including those proposed by SAMHSA and those currently in use in the U.K. Oral fluid samples (n = 1271) were collected prior to and following controlled clinical cocaine administration. CRS provides a qualitative screen at a preset cutoff of 30 microg/L. Sensitivity, specificity, and efficiency for CRS (30 microg/L) as compared with COC ELISA with a cutoff of 30 microg/L were 92.1%, 91.8%, and 92.0%. The comparison of CRS (30 microg/L) with the 8-mg/L proposed SAMHSA confirmation cutoffs for cocaine and/or benzoylecgonine exhibited a sensitivity of 82.7%, a specificity of 94.5%, and an efficiency of 87.6%. For this study, an alternative CRS cutoff of 20 microg/L was also evaluated. Performance characteristics of CRS (20 microg/L) at the proposed SAMHSA confirmation cutoffs were 89.9%, 89.7%, and 89.8%, respectively. At cutoffs in use in the U.K., 30- micro g/L CRS screen and 15- microg/L GC-MS cutoffs for cocaine, benzoylecgonine, and/or ecgonine methyl ester sensitivity, specificity, and efficiency were 89.4%, 92.2%, and 90.7%, respectively. Cozart RapiScan had performance similar to the COC ELISA assay for the detection of cocaine exposure and suitable sensitivity and specificity at the proposed SAMHSA cutoffs.

Cocaine↗

Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers.

BACKGROUND: Methamphetamine (METH) and amphetamine (AMP) concentrations in 200 plasma and 590 oral fluid specimens were used to evaluate METH pharmacokinetics and pharmacodynamics after oral administration of sustained-release METH. METHODS: Eight participants received four oral 10-mg S-(+)-METH hydrochloride sustained-release tablets within 7 days. Three weeks later, five participants received four oral 20-mg doses. Blood samples were collected for up to 24 h and oral fluid for up to 72 h after drug administration. RESULTS: After the first oral dose, initial plasma METH detection was within 0.25-2 h; c(max) was 14.5-33.8 micro g/L (10 mg) and 26.2-44.3 micro g/L (20 mg) within 2-12 h. In oral fluid, METH was detected as early as 0.08-2 h; c(max) was 24.7-312.2 micro g/L (10 mg) and 75.3-321.7 micro g/L (20 mg) and occurred at 2-12 h. The median oral fluid-plasma METH concentration ratio was 2.0 across 24 h and was highly variable. Neutral cotton swab collection yielded significantly higher METH and AMP concentrations than citric acid candy-stimulated expectoration. Mean (SD) areas under the curve for AMP were 21% +/- 25% and 24% +/- 11% of those observed for METH in plasma and oral fluid, respectively. After a single low or high dose, plasma METH was >2.5 micro g/L for up to 24 h in 9 of 12 individuals (mean, 7.3 +/- 5.5 micro g/L at 24 h); in oral fluid the detection window was at least 24 h (mean, 18.8 +/- 18.0 micro g/L at 24 h). The plasma and oral fluid 24-h METH detection rates were 54% and 60%, respectively. After four administrations, METH was measurable for 36-72 h (mean, 58.3 +/- 14.5 h). CONCLUSIONS: Perceived advantages of oral fluid for verifying METH exposure compared with urine include simpler specimen collection and reduced potential for adulteration, but urine offers higher analyte concentrations and a greater window of detection.

Administration, Oral↗

Urinary cannabinoid detection times after controlled oral administration of delta9-tetrahydrocannabinol to humans.

BACKGROUND: Urinary cannabinoid excretion and immunoassay performance were evaluated by semiquantitative immunoassay and gas chromatography-mass spectrometry (GC/MS) analysis of metabolite concentrations in 4381 urine specimens collected before, during, and after controlled oral administration of tetrahydrocannabinol (THC). METHODS: Seven individuals received 0, 0.39, 0.47, 7.5, and 14.8 mg THC/day in this double-blind, placebo-controlled, randomized, clinical study conducted on a closed research ward. THC doses (hemp oils with various THC concentrations and the therapeutic drug Marinol) were administered three times daily for 5 days. All urine voids were collected over the 10-week study and later tested by Emit II, DRI, and CEDIA immunoassays and by GC/MS. Detection rates, detection times, and sensitivities, specificities, and efficiencies of the immunoassays were determined. RESULTS: At the federally mandated immunoassay cutoff (50 microg/L), mean detection rates were <0.2% during ingestion of the two low doses typical of current hemp oil THC concentrations. The two high doses produced mean detection rates of 23-46% with intermittent positive tests up to 118 h. Maximum metabolite concentrations were 5.4-38.2 microg/L for the low doses and 19.0-436 micro g/L for the high doses. Emit II, DRI, and CEDIA immunoassays had similar performance efficiencies of 92.8%, 95.2%, and 93.9%, respectively, but differed in sensitivity and specificity. CONCLUSIONS: The use of cannabinoid-containing foodstuffs and cannabinoid-based therapeutics, and continued abuse of oral cannabis require scientific data for accurate interpretation of cannabinoid tests and for making reliable administrative drug-testing policy. At the federally mandated cannabinoid cutoffs, it is possible but unlikely for a urine specimen to test positive after ingestion of manufacturer-recommended doses of low-THC hemp oils. Urine tests have a high likelihood of being positive after Marinol therapy. The Emit II and DRI assays had adequate sensitivity and specificity, but the CEDIA assay failed to detect many true-positive specimens.

Administration, Oral↗

Sensitivity and specificity of the Cozart microplate EIA cocaine oral fluid at proposed screening and confirmation cutoffs.

BACKGROUND: Oral fluid is currently being evaluated as an alternative matrix for monitoring illicit drugs in federally mandated workplace drug testing, for addiction treatment programs, and for driving under the influence testing. The sensitivity, specificity, and efficiency of the Cozart Microplate EIA Cocaine Oral Fluid Kit (COC ELISA) were determined by comparison with gas chromatography-mass spectrometry (GC/MS) results at screening and confirmation cutoffs proposed in the US and UK. METHOD: Oral fluid was collected by expectoration after citric acid candy stimulation or with Salivette neutral cotton swabs or Salivette citric acid-treated cotton swabs before and after cocaine (COC) administration. Specimens (n = 1468) were analyzed with the COC ELISA for screening and with solid-phase extraction followed by GC/MS for confirmation. Three screening cutoffs (10, 20, and 30 microg/L) and four GC/MS cutoffs (2.5, 8, 10, and 15 microg/L COC, benzoylecgonine, and/or ecgonine methyl ester) were evaluated. GC/MS limit of quantification was 2.5 micro g/L for all analytes. RESULTS: COC ELISA interassay imprecision (CV; n = 19) was 16% at 16.7 microg/L and 12% at 81.8 microg/L. With the 2.5, 8, 10, and 15 microg/L GC/MS cutoffs, 59.0%, 54.7%, 52.7%, and 48.7% of the oral fluid specimens were positive, respectively. Sensitivity, specificity, and efficiency were 92.2%, 84.7%, and 88.8%, respectively, for the suggested Substance Abuse and Mental Health Services Administration (SAMHSA) cutoffs and 90.2%, 89.2%, and 89.7% for cutoffs currently used in the UK. CONCLUSIONS: COC ELISA had suitable sensitivity, specificity, and efficiency for identifying COC exposure at both the proposed SAMHSA and UK cutoffs. Sensitivity, specificity, and efficiency were >84% for both cutoffs, but 92 additional true-positive samples were identified with the SAMHSA cutoffs.

Adult↗

The state of office-based interventions for youth tobacco use.

Tobacco use is a serious pediatric health issue as dependence begins during childhood or adolescence in the majority of tobacco users. Primary care settings provide tremendous opportunities for delivering tobacco treatment to young tobacco users. Although evidence-based practice guidelines for treating nicotine dependence in youths are not yet available, professional organizations and the current clinical practice guideline for adults provide recommendations based on expert opinion. This article reports on the current tobacco treatment practices of pediatric and family practice clinicians, discusses similarities and differences between adolescent and adult tobacco use, summarizes research efforts to date and current cutting-edge research that may ultimately help to inform and guide clinicians, and presents existing recommendations regarding treating tobacco use in youths. Finally, recommendations are made for the primary care clinician, professional organizations, and health care systems and policies. Pediatricians and other clinicians can and should play an important role in treating tobacco dependence in youths.

Adolescent↗

Research on tobacco use among teenagers: ethical challenges.

Recent increases in adolescent smoking portend upcoming public health challenges as the majority of smokers initiate long-term addiction during youth, but experience major health consequences later in life. To effectively address this important teenage and adult health issue, critical research information and early interventions are needed, yet conducting tobacco research with teen smokers poses substantial challenges, including several ethical dilemmas. This paper reviews some of the ethical issues presented in etiologic and clinical treatment research addressing adolescent smoking. Common problems and possible solutions are presented. Issues of parent/guardian involvement, decision-making ability of teens, the need to maintain confidentiality are discussed, along with the specific problems of recruitment, compensation, and ethical challenges that arise in group treatment settings. Context-specific ethical adjustments and alternative perspectives are likely to be needed if we are to overcome procedural difficulties in conducting teen smoking studies.

Adolescent↗

Nicotine delivery from smoking bidis and an additive-free cigarette.

The present study was conducted to determine whether smoking bidis, an additive-free cigarette, and conventional cigarettes caused similar biochemical, physiological and subjective effects. This was an open-label, within-subject design. In each session, subjects (n = 10) smoked a single cigarette: an unfiltered Natural American Spirit, an unfiltered Irie bidi, an unfiltered Sher bidi, or one of the participant's own brand. The presentation of the cigarettes was randomized. Before and up to 1 h after smoking, biochemical markers [plasma nicotine levels and exhaled carbon monoxide (CO)] and physiological effects of nicotine (heart rate and blood pressure) were measured. After smoking, subjects completed two standardized tests of cigarette liking and cigarette sensations. American Spirit (32.1 ng/ml) and Irie bidi (26.0 ng/ml) cigarettes increased plasma nicotine more than the participant's own brand (18.5 ng/ml). Subjects smoked longer and took more puffs to consume the American Spirit (452.8 s, 14 puffs) and Sher bidi (354.4 s, 14 puffs) than the participant's own brand (297.4 s, 10 puffs). In spite of differences in nicotine delivery, participants rated all cigarettes as similar in nicotine content. Overall, the results indicate that bidis and the additive-free cigarette delivered nicotine, CO and (presumably) other toxic components of tobacco smoke in equal or greater amounts than conventional cigarettes. These results do not support an emerging belief that bidi cigarettes are safer than conventional brands.

Adult↗

Urinary elimination of cocaine metabolites in chronic cocaine users during cessation.

We previously showed that chronic cocaine use by active illicit users produced a longer plasma half-life than expected based on acute low-dose cocaine studies. Here we report urinary excretion patterns of cocaine metabolites as benzoylecgonine (BE) equivalents from 18 of the same individuals, housed for up to 14 days on a closed research unit. In addition, we evaluated whether creatinine normalization of BE equivalents increased mean detection time and reduced mean within-subject variability. All urine voids (N = 953) were individually assayed; BE equivalents were determined semi-quantitatively by FPIA. Compared to concentration in first void after admission, BE equivalents decreased to approximately 33%, 8%, and 4% at 24, 48, and 72 h, respectively. Mean +/- SD (range) time to first negative specimen (BE equivalents < 300 ng/mL) was 43.6 +/- 17.1 (16-66) h. BE equivalents fluctuated considerably across successive specimens; 69% of participants tested positive at least once after testing negative, and the mean time to last positive specimen was 57.5 +/- 31.6 (11-147) h after the first specimen. Thus, mean cocaine metabolite detection times were consistent with prolonged elimination, with 63% of participants testing positive longer than the expected 48-h window of detection after admission to the unit. Mean time to last positive after last use of cocaine, known by self-report only, was approximately 81 +/- 34 (34-162) h. Creatinine normalization, with the cut-off of 300 ng BE equivalents/mg creatinine, increased detection time: mean time to first negative specimen was 54.8 +/- 20.7 (20-100) h, and mean time to last positive specimen was 88.4 +/- 51.0 (35.6-235) h. Compared with the concentration in the first void after admission, BE equivalents/creatinine decreased to approximately 56%, 6%, and 5% at 24, 48, and 72 h. However, creatinine normalization did not reduce the fluctuation of BE equivalents across successive specimens. Thus, creatinine normalized values may be useful when the goal is to maximize the probability or duration of cocaine metabolite detection, but may be less useful in determining whether an individual has used cocaine since a previous specimen collection.

Adult↗

Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine administration.

BACKGROUND: The ease, noninvasiveness, and safety of oral fluid collection have increased the use of this alternative matrix for drugs-of-abuse testing; however, few controlled drug administration data are available to aid in the interpretation of oral fluid results. METHODS: Single oral codeine doses (60 and 120 mg/70 kg) were administered to 19 volunteers. Oral fluid and plasma were analyzed for free codeine, norcodeine, morphine, and normorphine by solid-phase extraction combined with gas chromatography-mass spectrometry (SPE/GC-MS). Physiologic and subjective effects were examined. RESULTS: Mean (SE) peak codeine concentrations were 214.2 +/- 27.6 and 474.3 +/- 77.0 micro g/L in plasma and 638.4 +/- 64.4 and 1599.3 +/- 241.0 micro g/L in oral fluid. The oral fluid-to-plasma ratio for codeine was relatively constant ( approximately 4) from 1 to 12 h. The mean half-life (t(1/2)) of codeine was 2.2 +/- 0.10 h in plasma and 2.2 +/- 0.16 h in oral fluid. Significant dose-related miosis and increases in sedation, psychotomimetic effect, and "high" occurred after the high dose. Mean codeine oral fluid detection time was 21 h with a 2.5 microg/L cutoff, longer than that of plasma (12-16 h). Detection times with the proposed Substance Abuse and Mental Health Services Administration cutoff (40 microg/L) were only 7 h. Norcodeine, but not morphine or normorphine, was quantified in both plasma and oral fluid. CONCLUSIONS: The disposition of codeine over time was similar in plasma and oral fluid, but because of high variability, oral fluid codeine concentrations did not reliably predict concurrent plasma concentrations. Oral fluid testing is a useful alternative matrix for monitoring codeine exposure with a detection window of 7-21 h for single doses, depending on cutoff concentrations. These controlled drug administration data should aid in the interpretation of oral fluid codeine results.

Administration, Oral↗

Duration of detectable methamphetamine and amphetamine excretion in urine after controlled oral administration of methamphetamine to humans.

BACKGROUND: Confirmation of a workplace drug test requires urinary methamphetamine (MAMP) and amphetamine (AMP) concentrations > or = 500 and 200 micro g/L, respectively, but cutoffs at half those values (250/100 micro g/L) have been proposed. We determined the urinary excretion of MAMP after oral ingestion and examined the effect of using lower cutoffs on detection of exposure. METHODS: Volunteers (n = 8) ingested four 10-mg doses of MAMP. HCl daily over 7 days, and five of them ingested four 20-mg doses 4 weeks later. After ingestion, the volunteers collected all urine specimens for 2 weeks. After solid-phase extraction, MAMP and AMP were measured by gas chromatography-positive chemical ionization mass spectrometry with dual silyl derivatization. RESULTS: MAMP and AMP were generally detected in the first or second void (0.7-11.3 h) collected after drug administration, with concentrations of 82-1827 and 12-180 micro g/L, respectively. Peak MAMP concentrations (1871-6004 micro g/L) after single doses occurred within 1.5-60 h. MAMP > or = 500 micro g/L was first detected in the first or second void (1-11 h) at 524-1871 micro g/L. Lowering the MAMP cutoff to 250 micro g/L changed the initial detection time little. AMP > or = 200 micro g/L was first detected in the 2nd-13th (7-20 h) post-administration voids. At a cutoff of 100 micro g/L, AMP was first confirmed in the second to eighth void (4-13 h). Reducing the cutoff to 250/100 micro g/L extended terminal MAMP detection by up to 24 h, increased total detection time by up to 34 h, and increased the total number of positive specimens by 48%. CONCLUSIONS: At the lower cutoff, initial detection times are earlier, detection windows are longer, and confirmation rates are increased. Elimination of the AMP requirement would increase detection rates and allow earlier detection.

Administration, Oral↗