Cocaethylene inhibits uptake of dopamine and can reach high plasma concentrations following combined cocaine and ethanol use.
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Alcoholic Intoxication↗
Biomedical subjects
P Jatlow
Publications and source records attributed to P Jatlow.
Determination of cocaine concentrations in plasma by high-performance liquid chromatography.
We describe a procedure for measuring concentrations of cocaine in plasma by reversed-phase high-performance liquid chromatography, with ion-pairing. The procedure involves solvent extraction followed by back-extraction with dilute acid. The n-propyl ester of benzoylecgonine is used as an internal standard. An evaporation step is not required, and concentrations as low as 5 micrograms/L can be quantified. Plasma concentrations of cocaine determined by high-performance liquid chromatography correlated well with those determined by a previously reported gas-chromatographic procedure with nitrogen detection.
Chromatography, Gas↗
Relationships of cyclosporine concentrations in serum, whole blood, and bile after renal and hepatic transplantation.
"Trough" (minimum inter-dose) cyclosporine concentrations were measured by liquid chromatography in samples of serum and whole blood or bile obtained from renal- and hepatic-transplant patients. Overall, concentrations in whole blood correlated poorly with concentrations in concurrently obtained serum. The poor correlation also held for individual patients over time. The degree of variability observed for individuals is especially disconcerting. Although cyclosporine measurements in whole blood may mitigate time- and temperature-dependent changes in the drug's distribution after collection, concentrations in serum separated after distribution are less dependent on the cellular mass in blood, and may better reflect the amount of drug available to receptor sites. This consideration may be particularly important in the postoperative period, when fluctuations in the cellular mass of blood are frequent. Concentrations of cyclosporine were also determined in concurrently collected bile and serum samples after liver transplantation. Concentrations of unchanged drug in bile were variably higher than those in serum. Bile/serum concentration ratios ranged from 65/1 to 4.6/1. It is postulated that bile/blood concentration ratios may reflect liver function.
Bile↗
Components of attention, methylphenidate dosage, and blood levels in children with attention deficit disorder.
In this study we analyzed some of the cognitive components that may constitute attention deficit disorder. It consisted of a double-blind, drug-placebo study of 12 children being treated with three doses of methylphenidate and placebo. Results of an attentional test battery, teacher and parent ratings, and blood levels of methylphenidate are reported. In general, performance was best with 0.6 mg/kg of methylphenidate (the highest dose tested) and worst with placebo. It is argued that no single test provides a complete assessment of attentional deficits and that methylphenidate can improve performance by affecting the allocation of cognitive resources to a task.
Adolescent↗
Therapeutic monitoring of psychotherapeutic drugs: role of the clinical laboratory.
Therapeutic monitoring of drugs is a well established clinical tool. However, the state of the art is somewhat less advanced for drugs used in psychiatry than it is for other classes of drugs, for several reasons. Most psychotherapeutic drugs have large volumes of distribution and achieve relatively low plasma concentrations following therapeutic doses. Many have one or more active metabolites. While psychotherapeutic drugs act through biochemical mechanisms, they are used to treat clinical syndromes which may be heterogeneous in their biochemical pathogenesis. As a consequence, the analytical methodologies are often complex and not always reliable; well-controlled clinical studies are difficult to perform; the therapeutic ranges have been difficult to establish. Despite these limitations, prudent and selective monitoring of serum drug concentrations, particularly of the tricyclic antidepressants, can be helpful in clinical management.
Antidepressive Agents, Tricyclic↗
Long-term amitriptyline in chronic depression.
Medication was discontinued under a placebo-controlled, double-blind, six-month protocol with 17 chronically depressed patients who had been taking an average daily dose of 138 mg amitriptyline (AMI) for an average of 3.7 years. Only one of nine patients became depressed on active medication, while of the 15 patients receiving a placebo trial, 11 had a depressive recurrence at an average time of 9.3 weeks. These 11 were subsequently restarted on AMI, and responded similarly to the way in which acutely depressed patients respond, although the patients showed either a need for less AMI or decreased symptoms, compared to entry. Tolerance did not develop to anticholinergic side-effects during long-term medication. Twelve of the 15 patients on placebo showed a withdrawal reaction during the first few weeks of tapered AMI discontinuation which could be distinguished from recurrence of depression. This study suggests that the majority of patients on long-term antidepressant will suffer a recurrence of depressive symptoms when the medication is discontinued.
Amitriptyline↗
Selection of analytic methods for therapeutic drug monitoring.
Selection of an analytic method for therapeutic drug monitoring usually involves an initial choice between chromatography and immunoassay. Once this decision has been made, numerous options remain within these two broad categories. There is no single correct or preferred assay technique. The best decision, based on technical, clinical, and economic considerations, will vary in different clinical and laboratory environments. The laboratory that has sufficient resources to maintain more than one type of technology will have a greater degree of flexibility in solving special problems.
Chromatography↗
Quantification of alprazolam in serum or plasma by liquid chromatography.
A reversed-phase "high-performance" liquid-chromatographic assay for the quantification of alprazolam in serum or plasma is described. Serum or plasma is extracted with toluene/isoamyl alcohol (99/1 by vol), evaporated, and reconstituted in the mobile phase. The latter is washed with hexane, then subjected to reversed-phase liquid chromatography and ultraviolet detection at 202 nm. Either U-31485, an alprazolam analog, or lorazepam, a 3-hydroxybenzodiazepine, is satisfactory as internal standards. Major alprazolam metabolites and various other commonly used drugs do not interfere. The useful lower limit of sensitivity for quantification is 2.5 micrograms/L. Peak height and alprazolam concentration are linearly related from 2.5 to 100 micrograms/L. For 10 and 20 micrograms/L concentrations, within-run CVs were 1.4% and 0.9% and the between-runs CVs 4.8% and 3.2%. Steady-state serum concentrations ranged from 25 to 55 micrograms/L in patients taking 1.5 to 6.0 mg per day, orally. Preliminary data suggest the method is also suitable for analysis of the structurally similar triazolobenzodiazepine, triazolam.
Alprazolam↗
Contact exposure to elemental iron causing chromonychia.
An orange-brown chromonychia developed on the toenails of a woman after a geographic move resulted in exposure to rural well water. Samples of the water and qualitative and quantitative examination of nail clippings confirmed the fact that the source for the discoloration was contact exposure to elemental iron. Installation of water purification equipment resulted in resolution of the nail stain over a six-week period of time.
Adult↗
Diazo-based assay for total bilirubin in a coated thin film evaluated.
We compared results for total bilirubin as measured on a coated thin film and by the Evelyn-Malloy and Jendrassik-Gróf methods. We examined serum samples from patients and studied the effects of protein, hemoglobin, and lipids on bilirubin measurement. Results from the thin-film assay compared favorably with those of the other methods. Total and within-day precision (CV), assessed over a one-year period, were better than 6% and 3%, respectively, at all concentrations. Analytical recovery was 99 +/- 3%. Samples from individuals having a wide range of liver diseases demonstrated, by linear regression, good correlation between the thin-film method and the two wet-chemistry methods (correlation coefficients of 0.990 and 0.994). We conclude that the thin-film method offers a valid alternative assay for total bilirubin.
Adult↗
The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia.
A directly reacting fraction of bilirubin that is probably covalently bound to albumin (albumin-bound bilirubin) has recently been described. To determine its clinical importance we used a new high-performance liquid-chromatography technique to measure it in the serum of 200 patients with hyperbilirubinemia from various causes. Albumin-bound bilirubin was an important fraction (8 to 90 per cent) of total bilirubin in patients with hepatocellular and cholestatic jaundice as well as in patients with the Dubin-Johnson syndrome. It was not detected in normal volunteers, neonates with physiologic jaundice, or patients with Gilbert's disease or hemolysis. Thus, albumin-bound bilirubin appears in serum when hepatic excretion of conjugated bilirubin is impaired. It becomes a larger component of serum bilirubin as jaundice subsides, delaying resolution of this disorder and causing bilirubin to persist in plasma after it has disappeared from the urine.
Bilirubin↗
Plasma cocaine concentrations during cocaine paste smoking.
Cigarettes containing cocaine paste were administered to experiences volunteer smokers in Peru, and plasma concentrations of cocaine were measured. Cocaine concentrations as high as 462 ng/ml were obtained after only three minutes of smoking cocaine paste. Subjects titrated their rate of consumption so as to achieve remarkably constant plasma concentrations during the smoking period. Areas under curve (AUC), adjusted for dose, were approximately 70% that obtained with oral or intranasal administration of cocaine to different subjects in previous experiments.
Adult↗
Desipramine plasma concentration and antidepressant response.
The relationship of desipramine hydrochloride plasma concentration and antidepressant response was determined in 30 depressed inpatients treated for three weeks with desipramine. All patients had a nondelusional unipolar depression, met DSM-III criteria for major depressive episode with melancholia, and had a Hamilton score of 18 or greater after one week of hospitalization without medication. Eighty-nine percent of the patients with plasma concentrations above 115 ng/mL responded, in contrast to 14% of those with concentrations below this level, a significant difference (Fisher's exact test, P less than .001). Ten initial nonresponders were converted to responders when dosage increase raised desipramine plasma concentration to 125 ng/mL or above. In clinical practice a plasma concentration of 125 ng/mL would be a useful guideline as a threshold above which desipramine is likely to be effective.
Depressive Disorder↗
Kinetics of drug effect by distributed lags analysis: an application to cocaine.
The same plasma drug concentration may induce different effects depending on whether the concentration is rising or falling. We described a new method of modeling kinetics of drug effects that can handle such "dissociation" phenomena, that does not depend on compartmental theory, and that allows quantitative comparisons between experiments. As applied to cocaine, it is shown that the resulting models are independent of drug dose or route of administration and give good predictions of the time course of response.
Administration, Intranasal↗
Steady-state plasma concentrations of cis- and trans-10-OH amitriptyline metabolites.
Plasma concentrations of the geometric isomers of 10-OH amitriptyline (10-OH AT) and 10-OH nortriptyline (10-OH-NT) were determined by reversed-phase high-pressure liquid chromatography. Steady-state concentrations of At, NT, and the four 10-OH metabolites were measured in 27 patients taking AT for depression. All of the unconjugated hydroxylated metabolites were usually detectable and trans-10-OH NT always predominated. Mean concentrations, expressed as percentage of the sum of all six compounds, were: AT 30%, NT 27%, cis-10-OH AT 1.1%, trans-10-OH AT 4.0%, cis-10-OH NT 4.0%, and trans-10-OH NT 33%. Repeated measurements on 10 patients over several weeks indicated that interindividual variations in absolute and relative 10-OH metabolite concentrations are much greater than day-to-day variations. Five patients who also received a phenothiazine had a lower proportion of 10-OH metabolites.
Adult↗
Recurrence of depression after discontinuation of long-term amitriptyline treatment.
In this study 10 of 17 patients receiving long-term amitriptyline treatment (average duration: 3.7 years, average dose: 138 mg) had their medication tapered and discontinued under double-blind conditions. Eight became depressed within 3 to 15 weeks. None of the 7 control subjects became depressed during the 6 months of the study. Those who became depressed also showed psychomotor retardation and sleep disturbance. Relief of longstanding anticholinergic side effects followed medication discontinuation. Some patients whose amitryptyline was discontinued experienced a mild withdrawal syndrome within the first 2 weeks, consisting of irritability, dream and sleep disturbance, and restlessness during the first few weeks.
Adult↗
Intranasal cocaine: dose relationships of psychological effects and plasma levels.
We compared the psychological effects of three doses of intranasal cocaine hydrochloride (.2, .75, and 1.5 mg/kg) with cocaine plasma concentrations in four volunteers. Intranasal lidocaine hydrochloride (.2 mg/kg) was used as a topically active placebo. Peak "high" ratings were related to both dose and peak plasma concentrations. At a given plasma concentration, "high" ratings were greater when plasma levels were increasing than when they were decreasing. This indicates that acute tolerance by tachphylaxis occurred after single doses. The cocaine "high" was a pleasant feeling but was without distinctive sensations. The dramatic effects of intranasal cocaine on the street may be related to larger or repeated doses as well as the setting.
Administration, Intranasal↗
Psychopharmacology of attention deficit disorder: pharmacokinetic, neuroendocrine, and behavioral measures following acute and chronic treatment with methylphenidate.
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Attention Deficit Disorder with Hyperactivity↗