scholarly journals Disposition of Cocaine and Its Metabolites in Human Sweat after Controlled Cocaine Administration

2005 ◽  
Vol 51 (11) ◽  
pp. 2085-2094 ◽  
Author(s):  
Sherri L Kacinko ◽  
Allan J Barnes ◽  
Eugene W Schwilke ◽  
Edward J Cone ◽  
Eric T Moolchan ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Gas Chromatography Mass Spectrometry ◽  
Low Doses ◽  
Cocaine Exposure ◽  
Limit Of Quantification ◽  
Noninvasive Technique ◽  
Monitoring Drug ◽  
Significant Difference ◽  
Sweat Testing ◽  
High Doses

Abstract Background: Sweat testing is a noninvasive technique for monitoring drug exposure in treatment, criminal justice, and employment settings. Methods: We evaluated cocaine excretion in 9 participants’ sweat after they received 3 low doses (75 mg/70 kg) of cocaine HCl subcutaneously within 1 week and, 3 weeks later, 3 high doses (150 mg/70 kg). Six additional participants completed portions of the study. PharmChek® sweat patches (n = 1390) were collected throughout a 3-week washout period, reflecting previously self-administered drugs, and during and after controlled dosing. Results: Cocaine was the primary analyte detected with 24% of patches positive at the gas chromatography–mass spectrometry limit of quantification of 2.5 ng/patch and 7% of patches at the proposed Substance Abuse and Mental Health Services Administration cutoff of 25 ng/patch. Ecgonine methyl ester (EME) was detected more often and at generally higher concentrations than benzoylecgonine. In patches containing both metabolites, there was no statistically significant difference in the benzoylecgonine/EME ratio based on length of patch wear. During washout, 2 participants’ weekly patches tested positive (≥25 ng/patch) during the first week; one remained positive during week 2; and none were positive during week 3. Cocaine and EME were detectable within 2 h; benzoylecgonine was not detected until 4–8 h after low doses and slightly sooner after high doses. The majority of drug was excreted within 24 h. Over 70% of weekly patches worn during low doses were positive for cocaine (≥25 ng/patch), increasing to 100% during high doses. Conclusion: Sweat testing is an effective and reliable method of monitoring cocaine exposure.

scholarly journals Methimazole and Propylthiouracil Equally Cross the Perfused Human Term Placental Lobule*

1997 ◽  
Vol 82 (9) ◽  
pp. 3099-3102 ◽  
Author(s):  
R. H. Mortimer ◽  
G. R. Cannell ◽  
R. S. Addison ◽  
L. P. Johnson ◽  
M. S. Roberts ◽  
...  
Keyword(s):  
Compartmental Model ◽  
Placental Transfer ◽  
Low Doses ◽  
Bovine Albumin ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Fetal Thyroid ◽  
Drug Doses ◽  
Model Transfer ◽  
High Doses

Abstract Propylthiouracil (PTU) is widely believed to cross the placenta less freely than methimazole (MMI) and is therefore regarded as the preferred drug for treatment of hyperthyroidism in pregnancy. Clinical studies comparing the two drugs show, however, no differences in maternal or fetal thyroid function. We investigated transfer from the maternal to the fetal circuit in the isolated perfused term human placental lobule of low and high doses of PTU (4 μg/mL and 40μ g/mL) and MMI (1.5 μg/mL and 15 μg/mL) in protein-free perfusate and low doses of both drugs with addition of 40 g/L of bovine albumin. Both drugs readily crossed the placenta, reaching equilibrium in all experiments in about 2 h. Drug concentrations in the two circuits fitted a two compartmental model. Transfer kinetics for the two drugs were similar, nonsaturable, and unaffected by addition of albumin. Clearances (mL·min−1·g−1, means ± sd) of PTU from maternal to fetal circuits were: 0.229± 0.110, 0.216 ± 0.065, and 0.170 ± 0.032; and for transfer of MMI: 0.165 ± 0.025, 0.232 ± 0.153, and 0.174 ± 0.009 (for low doses without, low doses with, and high doses without albumin, respectively). Clearances of PTU from fetal to maternal circuits were: 0.147 ± 0.072, 0.109 ± 0.014, and 0.116 ± 0.028; and for transfer of MMI: 0.095 ± 0.029, 0.122 ± 0.088, and 0.12 ± 0.005 (in the same experiments). There was no significant difference between drugs or drug doses and no effect of addition of albumin. We conclude that PTU and MMI have similar placental transfer kinetics.

Information Processing and Developmental Assessments in 3-Month-Old Infants Exposed Prenatally to Cocaine

PEDIATRICS ◽  
1995 ◽  
Vol 95 (4) ◽  
pp. 539-545
Author(s):  
Linda C. Mayes ◽  
Marc H. Bornstein ◽  
Katarzyna Chawarska ◽  
Richard H. Granger
Keyword(s):  
Information Processing ◽  
Infant Development ◽  
Drug Exposure ◽  
Sociodemographic Factors ◽  
Cocaine Exposure ◽  
Prenatal Cocaine Exposure ◽  
Significant Difference ◽  
Prenatal Cocaine ◽  
Developmental Index ◽  
Developmental Assessments

Objective. To determine the effect of prenatal cocaine exposure on 3-month infant information processing and developmental assessments. Methods. One hundred and eight infants, 61 cocaine-exposed and 47 controls, participated at 3 months of age in an infant-control habituation and novelty responsiveness procedure and in a developmental assessment using the Bayley Scales of Infant Development both administered by experimenters blind to the drug exposure status of the infant. Results. Compared to the non-drug-exposed group, infants exposed prenatally to cocaine were significantly more likely to fail to start the habituation procedure and, for those who did, significantly more likely to react with irritability early in the procedure. The majority of infants in both groups reached the habituation criterion, and among those who did there were no significant difference between cocaine and non-cocaine-exposed infants in habituation or in recovery to a novel stimulus. Infants who were cocaine-exposed showed comparatively depressed performance on the motor (Psychomotor Developmental Index) but not the mental (Mental Developmental Index (MDI)) scales of the Bayley. These results obtained for habituation and Bayley MDI controlling for both perinatal and sociodemographic factors. Conclusions. Differences in reactivity to novelty but not in information processing between cocaine-exposed and non-cocaine-exposed infants suggest that the effects of prenatal cocaine exposure may be on arousal and attention regulation rather than early cognitive processes.

scholarly journals Opioid Disposition in Human Sweat after Controlled Oral Codeine Administration

2006 ◽  
Vol 52 (8) ◽  
pp. 1539-1545 ◽  
Author(s):  
Eugene W Schwilke ◽  
Allan J Barnes ◽  
Sherri L Kacinko ◽  
Edward J Cone ◽  
Eric T Moolchan ◽  
...  
Keyword(s):  
Drug Testing ◽  
Solid Phase ◽  
Gas Chromatography Mass Spectrometry ◽  
High Dose ◽  
Opioid Use ◽  
Complex Processes ◽  
Sweat Testing ◽  
High Doses ◽  
Sweat Tests

Abstract Background: Characterization of opioid excretion in sweat is important for accurate interpretation of sweat tests in drug treatment, criminal justice, and workplace drug testing programs. Methods: Participants (n = 20) received placebo, 3 low (60 mg/70 kg) or 3 high (120 mg/70 kg) codeine sulfate doses (used as a model for opioid excretion) within 1 week. Codeine and metabolites in sweat were collected with PharmChek® Sweat Patches; hourly patches were applied for 1 to 15 h (n = 775) and weekly patches for 7 days (n = 118). Patches were analyzed by solid-phase extraction and gas chromatography–mass spectrometry for codeine, norcodeine, morphine, normorphine, and 6-acetylmorphine. Limits of quantification were 2.5 ng/patch (codeine and morphine) and 5 ng/patch (other analytes). Results: Codeine was the only analyte identified in 12.6% of hourly patches and 83.3% of weekly sweat patches worn during dosing. Weekly patch concentrations (SD) were 38.6 (59.9) ng/patch [median (range), 15.9 (0–225.1) ng/patch] for low and 34.1 (32.7) ng/patch [24.0 (0–96.2) ng/patch] for high codeine doses. Codeine detected 1 week after dosing was 4.6 (5.3) ng/patch [median (range), 4.0 (0–17.1) ng/patch; n = 11] after low and 7.7 (7.1) ng/patch [6.9 (0–20.5) ng/patch; n = 10] after high doses. In total, 2.6% of hourly, 38.5% of low-dose, and 45.5% of high-dose weekly patches contained codeine at the proposed Substance Abuse and Mental Health Services Administration cutoff. Conclusions: Codeine was the only analyte detected, at highly variable concentrations, up to 2 weeks after dosing. These results are consistent, considering the complex processes of codeine deposition in sweat. Sweat testing is a useful alternative technique for qualitative monitoring of opioid use.

scholarly journals Effect of low dose ASV with supportive care in poisonous snake bites in Marathwada region, Aurangabad, Maharashtra, India

2015 ◽  
Vol 1 (8) ◽  
pp. 307
Author(s):  
Mangala S. Borkar ◽  
Chandrakant G. Lahane ◽  
Akshay A. Kashid ◽  
Swati U. Chavan ◽  
Sandeep G. Uppod
Keyword(s):  
Low Dose ◽  
Fresh Frozen Plasma ◽  
Average Dose ◽  
Low Doses ◽  
Number Of Patients ◽  
Snake Bites ◽  
Significant Difference ◽  
Male Preponderance ◽  
Fresh Frozen ◽  
High Doses

<p class="abstract"><strong>Background:</strong> Due to a large number of patients and severe scarcity of ASV with patches of unavailability and unaffordable high cost, low doses of ASV had to be compulsorily used for treatment of poisonous snakebites. The main objective is to study the effectiveness of low dose ASV (total &lt;50 ml) in the management of poisonous snake bites in the scenario of global ASV scarcity.</p><p class="abstract"><strong>Methods:</strong> Patients of snake bites with signs of envenomation were included in this observational, prospective study. Immediately, low dose (30 to 50 ml) of ASV was started after carefully testing intravenously. The patients were kept under intensive observation with supportive management (artificial ventilation, neostigmine-atropine, blood and fresh frozen plasma, as needed).  </p><p class="abstract"><strong>Results:</strong> In the study of 309 patients, slight male preponderance was seen (161 males and 148 females).144 patients had vasculotoxic, 122 patients had neurotoxic and 43 patients had mixed type (both vasculotoxic and neurotoxic) of envenomation. Average dose of ASV given was 35.30 ml. 297 patients survived, 12 died. In 42 cases having both neurological and vasculotoxic (mixed) snake bite, 7 patients (16.66%) died. Among 122 neuroparalytic cases, 5 (4.0983%) died. We did not get any mortality in the 145 cases of vasculotoxic snake bites. There was no statistically significant difference in the outcome of the patients whether they received higher or low doses of ASV.</p><strong>Conclusions:</strong> There was no significant difference in the outcome of poisonous snake bites whether low dose (&lt;50 ml) or high doses (&gt;50 ml) of ASV were given and practically all the victims who came on time, survived with low doses of ASV. This is very important in developing countries like India where there is high incidence of poisonous snake bites and scarcity of ASV.

Markers of Hemostatic Activation in Affected Coronary Arteries during Angioplasty

1994 ◽  
Vol 72 (05) ◽  
pp. 672-675 ◽  
Author(s):  
Nicolas W Shammas ◽  
Michael J Cunningham ◽  
Richard M Pomearntz ◽  
Charles W Francis
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Venous Blood ◽  
Balloon Inflation ◽  
Blood Samples ◽  
Hemostatic System ◽  
Significant Difference ◽  
Hemostatic Markers ◽  
Artery Disease ◽  
High Doses

SummaryTo characterize the extent of early activation of the hemostatic system following angioplasty, we obtained blood samples from the involved coronary artery of 11 stable angina patients during the procedure and measured sensitive markers of thrombin formation (fibrino-peptide A, prothrombin fragment 1.2, and soluble fibrin) and of platelet activation ((3-thromboglobulin). Levels of hemostatic markers in venous blood obtained from 14 young individuals with low pretest probability for coronary artery disease were not significantly different from levels in venous blood or intracoronary samples obtained prior to angioplasty. Also, there was no translesional (proximal and distal to the lesion) gradient in any of the hemostatic markers before or after angioplasty in samples obtained between 18 and 21 min from the onset of the first balloon inflation. Furthermore, no significant difference was noted between angioplasty and postangioplasty intracoronary concentrations. We conclude that intracoronary hemostatic activation does not occur in the majority of patients during and immediately following coronary angioplasty when high doses of heparin and aspirin are administered.

ANTAGONISTIC ACTION OF NORETHYNODREL ON THE TESTOSTERONE-DEPENDENT PROCESS OF FRUCTOSE FORMATION IN MOUSE SEX ACCESSORY ORGANS

1966 ◽  
Vol 51 (2) ◽  
pp. 224-230 ◽  
Author(s):  
John A. Thomas ◽  
Edward T. Knych
Keyword(s):  
Antagonistic Activity ◽  
Low Doses ◽  
Antagonistic Action ◽  
Dependent Process ◽  
High Doses

ABSTRACT Norethynodrel antagonized the fructose stimulating effects of exogenous testosterone in sex accessory organs of castrate mice. It was antiandrogenic at both low doses (50 μg) and high doses (400 μg) of testosterone. Norethindrone and ethisterone suppressed fructose formation in the testosterone-treated castrate mouse, but not as effectively as norethynodrel. Norethandrolone exerted no antagonistic activity.

Cytidine Deaminase Residual Activity in Serum Is a Predictive Marker of Early Severe Toxicities in Adults After Gemcitabine-Based Chemotherapies

2010 ◽  
Vol 28 (1) ◽  
pp. 160-165 ◽  
Author(s):  
Joseph Ciccolini ◽  
Laetitia Dahan ◽  
Nicolas André ◽  
Alexandre Evrard ◽  
Muriel Duluc ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Cytidine Deaminase ◽  
Residual Activity ◽  
Predictive Marker ◽  
Adult Patients ◽  
Functional Testing ◽  
Simple Test ◽  
Increased Risk ◽  
Significant Difference ◽  
Patients At Risk

Purpose Anticipating toxicities with gemcitabine is an ongoing story, and deregulation in cytidine deaminase (CDA) could be associated with increased risk of developing early severe toxicities on drug exposure. Patients and Methods A simple test to evaluate CDA phenotypic status was first validated in an animal model investigating relationships between CDA activity and gemcitabine-related toxicities. Next, relevance of this test as a marker for toxicities was retrospectively tested in a first subset of 64 adult patients treated with gemcitabine alone, then it was tested in a larger group of 130 patients who received gemcitabine either alone or combined with other drugs and in 20 children. Additionally, search for the 435 T>C, 208 G>A and 79 A>C mutations on the CDA gene was performed. Results In mice, CDA deficiency impacted on gemcitabine pharmacokinetics and had subsequent lethal toxicities. In human, 12% of adult patients experienced early severe toxicities after gemcitabine administration. A significant difference in CDA activities was observed between patients with and without toxicities (1.2 ± 0.8 U/mg v 4 ± 2.6 U/mg; P < .01). Conversely, no genotype-to-phenotype relationships were found. Of note, the patients who displayed particularly reduced CDA activity all experienced strong toxicities. Gemcitabine was well tolerated in children, and no CDA deficiency was evidenced. Conclusion Our data suggest that CDA functional testing could be a simple and easy marker to discriminate adult patients at risk of developing severe toxicities with gemcitabine. Particularly, this study demonstrates that CDA deficiency, found in 7% of adult patients, is associated with a maximum risk of developing early severe toxicities with gemcitabine.

scholarly journals Antifertility Actions of a-Chlorohydrin in the Male

1983 ◽  
Vol 36 (4) ◽  
pp. 333 ◽  
Author(s):  
A RJones
Keyword(s):  
Male Fertility ◽  
Human Sperm ◽  
Male Rat ◽  
Low Doses ◽  
Dose Regime ◽  
Male Contraceptive ◽  
The Past ◽  
High Doses ◽  
Species Specific ◽  
Daily Oral Administration

Non-steroidal chemicals that affect male fertility have been known for over 25 years but only one compound, oc-chlorohydrin, possesses most of the attributes of an ideal male contraceptive. In the male rat, for example, continuous daily oral administration of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn. Such a dose regime does not interfere with libido, is apparently not toxic and the action is specific towards mature sperm. Furthermore, the action of the compound is species-specific: it is effective in the rat, ram, boar, guinea pig, hamster,rhesus monkey and upon ejaculated human sperm but it is ineffective in the mouse and the rabbit. High doses of oc-chlorohydrin can be neurotoxic, nephrotoxic and, in rats, lead to prolonged or permanent infertility. However, the antifertility response and the toxicity of racemic oc-chlorohydrin may be due, respectively, to the separate enantiomers. No other antifertility chemical has been investigated to such an extent as oc-chlorohydrin; this article reviews the progress that has been achieved with oc-chlorohydrin during the past six years.

Serological biomarkers of zearalenone exposure in beef heifers receiving anti-mycotoxin additive

2020 ◽  
pp. 1-10
Author(s):  
C. Tonini ◽  
M.S. Oliveira ◽  
E.B. Parmeggiani ◽  
D.A.F. Sturza ◽  
A.O. Mallmann ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Biological Fluids ◽  
Basal Diet ◽  
Beef Heifers ◽  
Efficacy Evaluation ◽  
Limit Of Quantification ◽  
In Vivo Measurement ◽  
Significant Difference ◽  
Serological Biomarkers

The inclusion of anti-mycotoxin additives (AMA) in the diet of production animals has been widely used to avoid mycotoxin exposure. In order to confirm the efficacy of such products in vivo, measurement of mycotoxins and/or their metabolites in biological fluids is preconized. This study aimed at determining the serological biomarkers of zearalenone (ZEN), α-zearalenol, β-zearalenol, α-zearalanol, β-zearalanol (β-ZAL) and zearalanone, to evaluate the efficacy of an AMA in beef heifers. The trial lasted 37 days: 11 days of adaptation, 21 days of actual experiment, and 5 days of regression. Twenty-four heifers were randomly assigned to receive one of the following treatments (n=6/group): (T1) basal diet (control); (T2) basal diet + 5 mg/kg of ZEN; (T3) basal diet + 5 mg/kg of ZEN + 2.5 kg/t of AMA; and (T4) basal diet + 5 mg/kg of ZEN + 5.0 kg/t of AMA. Blood sampling was performed on different days after the diet was given. The samples were centrifuged to obtain the blood serum, and then analysed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). β-ZAL was detected above the limit of quantification both in the unconjugated (>0.60 ng/ml) and conjugated (>0.90 ng/ml) forms. The remaining metabolites presented concentrations under the limit of detection. In the efficacy evaluation of the AMA, there was no significant difference (P>0.05) between the treatments with and without additive at the tested levels of inclusion. Thus, β-ZAL may be employed as a biomarker of ZEN exposure via diet to evaluate the efficacy of an AMA through serological parameters. The technique applied in this study proved to be an adequate alternative for in vivo confirmation of the efficacy of products in adsorbing the toxin.

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