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D N Bailey

Publications and source records attributed to D N Bailey.

At least 19 recordsLinked to original sources
PubMed2001

Effect of coadministered drugs and ethanol on the binding of therapeutic drugs to human serum in vitro.

The effects of coadministered drugs and ethanol on the binding of therapeutic drugs to human serum in vitro was investigated. Acetaminophen, lidocaine, phenobarbital, quinidine, theophylline, and valproic acid were added to pooled human serum at therapeutic concentrations. To each preparation was added one additional drug at three concentrations ranging from therapeutic to toxic. The following eight target drug/added drug combinations were studied: acetaminophen/phenobarbital. acetaminophen/theophylline, lidocaine/quinidine, phenobarbital/acetaminophen, phenobarbital/valproic acid, quinidine/lidocaine, theophylline/acetaminophen, and valproic acid/phenobarbital. Each serum without the other added drug as well as the serum supplemented with the other drug at the three concentrations was dialyzed against phosphate buffer. Similarly dialyzed were phenobarbital, quinidine, and theophylline, both alone at therapeutic concentrations in serum and with ethanol at three different concentrations in serum. The percentage of drug binding in each preparation was calculated. Acetaminophen diminished the binding of theophylline to human serum by a net change of 5.7% (percentage increase in free drug fraction [FDF], 11.0%) at 662 micromol/L and by a net change of 7.1% (percentage increase in FDF, 13.7%) at 1324 micromol/L. Theophylline decreased the binding of acetaminophen by a net change of 6.8% (percentage increase in FDF, 8.8%) at 277.5 micromol/L; phenobarbital reduced it by a net change of 6.6% (percentage increase in FDF, 8.5%) at 431 micromol/L. Valproic acid diminished binding of phenobarbital by a net change of 9.9% (percentage increase in FDF, 21.2%) at 1732 micromol/L. No significant effects were noted with other drug combinations or with the addition of ethanol. Coingestion of acetaminophen with theophylline, phenobarbital with acetaminophen, and valproic acid with phenobarbital at high to toxic concentrations decreases the binding of the target drug. The resulting increase in free drug concentration may lead to enhanced drug effect in vivo.

Blood Proteins↗
PubMed2000

Cocaine and cocaethylene binding to normal human brain and Alzheimer disease brain.

The binding of cocaine and cocaethylene to homogenates of both normal whole brain and whole brain with Alzheimer disease patients (Alzheimer brain) was investigated in vitro using equilibrium dialysis of the unlabelled drugs at 4 degrees C. Two binders of cocaine were characterized in normal brain (binder 1: Ka, 5.73 x 10(3) L/mol; Bo, 7.44 x 10(-5) mol/L) (binder 2: Ka, 1.54 x 10(3) L/mol; Bo, 2.50 x 10(-4) mol/L) and in Alzheimer brain (binder 1: Ka, 3.08 x 10(2) L/mol; Bo, 6.66 x 10(-4) mol/L) (binder 2: Ka, 8.74 x 10(1) L/mol; Bo, 4.30 x 10(-3) mol/L). For cocaethylene three binders were noted in normal brain (binder 1: Ka, 3.23 x 10(3) L/mol; Bo, 1.22 x 10(-4) mol/L) (binder 2: Ka, 3.10 x 10(3) L/mol; Bo, 2.01 x 10(-4) mol/L) (binder 3: Ka, 1.63 x 10(3) L/mol; Bo, 3.59 x 10(-4) mol/L) and two binders in Alzheimer brain (binder 1: Ka, 5.18 x 10(3) L/mol; Bo, 3.06 x 10(-5) mol/L) (binder 2: Ka, 3.36 x 10(3) L/mol; Bo, 7.75 x 10(-5) mol/L). The binding of cocaine to normal brain was much stronger than to Alzheimer brain (ten- to 100-fold), whereas the binding of cocaethylene was similar in normal and Alzheimer brain. Cocaine and cocaethylene binding to human brain was compared with cocaine and cocaethylene binding to other human tissues previously studied by this laboratory.

Aged↗
PubMed1999

Quinidine inhibition of cocaethylene degradation in human serum in vitro: a preliminary study.

Quinidine (QUINID) substantially inhibited the serum degradation of cocaethylene (CE), an important cocaine analog, when incubated for two hours at 37 degrees C with pooled human serum containing 1.58 micromol/L of CE. In the absence of QUINID, the CE concentration was only 49.4% of its original value after incubation. However, QUINID at subtherapeutic (3.08 micromol/L) and therapeutic (15.4 micromol/L) concentrations preserved 55.1% and 75.9% of the original CE concentration, respectively. At a QUINID concentration of 308 micromol/L, 89.2% of the CE concentration was preserved. There was a marked decrease in the serum cholinesterase (CHE) activity as QUINID concentrations were increased to 154 micromol/L (19.8% decrease in CHE) and to 308 micromol/L (36.8% decrease in CHE). These data suggest that QUINID inhibits the hydrolysis of CE in human serum by suppressing CHE activity. These findings are significant because QUINID may be used in patients who have abused cocaine with ethanol. They also have important implications for individuals receiving QUINID together with other drugs whose hydrolysis may be catalyzed by CHE.

Anti-Arrhythmia Agents↗
PubMed1998

Cocaine and cocaethylene binding to human milk.

The binding of cocaine and its ethyl analog, cocaethylene, to human milk was studied using equilibrium dialysis at 4 degrees C. For cocaine, a low-affinity, high-capacity binder was noted (equilibrium constant of association, Ka, 3.12 x 10(3) L/mol; concentration of binding sites, B0, 3.85 x 10(-4) mol/L), as well as a very low affinity, high-capacity binder (Ka, 7.54 x 10(2) L/mol; B0, 1.42 x 10(-3) mol/L). For cocaethylene, 2 low-affinity, high-capacity binders were suggested: a stronger (Ka, 3.79 x 10(3) L/mol; B0, 3.27 x 10(-4) mol/L) and a weaker (Ka, 1.84 x 10(3) L/mol; B0, 8.91 x 10(-4) mol/L) binder The low-affinity, high-capacity binder for cocaine and cocaethylene seems to be albumin, while the weaker nonspecific binding may be due to lipids. Up to 55% of cocaine and up to 61% of cocaethylene were bound to milk; such binding, coupled with the lower pH of milk (6.9) relative to that of serum (7.4), may enhance the mammary secretion of these 2 basic drugs, having important consequences for the nursing infant.

Cocaine↗
PubMed1998

Cocaine and cocaethylene binding to human liver.

The binding of cocaine (COC) and cocaethylene (CE) to whole human liver homogenates in vitro was studied by equilibrium dialysis. Drugs were measured by high-pressure liquid chromatography. Up to 32% of COC and up to 43% of CE were bound. Scatchard analysis suggested a high-affinity, low-capacity binder for both COC (Ka, 4.69 x 10(4) L/mol; Bo, 1.08 x 10(-5) mol/L) and CE (Ka, 4.38 x 10(4) L/mol; Bo, 1.54 x 10(-5) mol/L). In addition, low-affinity, high-capacity binders for COC (Ka, 2.93 x 10(3) L/mol; Bo, 1.32 x 10(-4) mol/L) and CE (Ka, 6.50 x 10(3) L/mol; Bo, 1.11 x 10(-4) mol/L) were noted. Finally, for both compounds, very low-affinity, high-capacity binding, which was likely nonspecific in nature, was defined as follows: COC, Ka, 8.00 x 10(2) L/mol; Bo, 5.45 x 10(-4) mol/L and CE, Ka, 2.10 x 10(3) L/mol; Bo, 3.71 x 10(-4) mol/L. The binding profiles of COC and CE in liver were compared with those in human serum and placenta studied previously by this laboratory.

Adult↗
PubMed1997

Cocaine and cocaethylene binding to human placenta in vitro.

OBJECTIVE: The aim of the study was to determine the binding profiles of cocaine and its ethyl homolog, cocaethylene, in human placenta. STUDY DESIGN: Pooled whole human placental homogenates supplemented with either nonlabeled cocaine or cocaethylene over the concentration range 10 to 5000 x 10(-7) mol/L were submitted for equilibrium dialysis. Drug concentrations were measured by high-pressure liquid chromatography. Scatchard analysis of the data was performed. RESULTS: A high-affinity, low-capacity binder was identified for cocaine (equilibrium constant of association, 3.68 x 10(5) L/mol; concentration of binding sites, 4.36 x 10(-6) mol/L) and for cocaethylene (equilibrium constant of association, 2.42 x 10(4) L/mol; concentration of binding sites, 2.65 x 10(-5) mol/L). Also, a low-affinity, high-capacity binder was noted for cocaine (equilibrium constant of association, 1.93 x 10(3) L/mol; concentration of binding sites, 5.28 x 10(-4) mol/L) and for cocaethylene (equilibrium constant of association, 2.15 x 10(2) L/mol; concentration of binding sites, 2.65 x 10(-3) mol/L). The concentration of binding sites expressed as moles per gram of placenta was as follows: high-affinity binder (cocaine, 4.36 x 10(-8); cocaethylene, 2.65 x 10(-7) and low-affinity binder (cocaine, 5.28 x 10(-6); cocaethylene, 2.65 x 10(-5). Up to 59% of cocaine and up to 42% of cocaethylene was bound. CONCLUSION: Human placenta may serve as a depot for cocaine and cocaethylene.

Binding Sites↗
PubMed1997

Effect of drugs and cocaine metabolites on cocaine and cocaethylene binding to human serum in vitro.

The effect of amphetamine (AMPH), codeine (COD), methamphetamine (MEPH), morphine (MORP), and benzoylecgonine (BE) on the binding of cocaethylene (CE) and cocaine (COC) to human serum in vitro was investigated by equilibrium dialysis at 4 degrees C. Each compound was added individually at concentrations of 500, 1,000, or 2,000 nM to pooled human serum containing COC or CE at 500 nM concentration. For COC, the addition of COD, MEPH, and CE enhanced serum binding whereas MORP and BE decreased it. Variable effects on COC binding were noted for AMPH. For CE, the addition of COD and COC generally increased binding whereas MORP decreased it. No appreciable effect on CE binding was observed after adding AMPH, MEPH, and BE. Except for CE, AMPH, and MEPH in the presence of COC, the binding of COC and CE tended to be less with 2,000 nM of each added drug than at lower concentrations of them, presumably because of mass-action displacement of COC and CE at the higher concentration. These findings should be clinically important because these drugs are frequently found together in patients.

Amphetamine↗
PubMed1996

Results of limited versus comprehensive toxicology screening in a university medical center.

Both comprehensive toxicology screening (COM) and limited toxicology screening (LIM) were performed on the same urine in 1,734 consecutive cases over a 6-month period at a university medical center. About half of the screens originated from inpatient services and half from outpatient services (mostly emergency department). In 71 % of the cases, there was agreement between the results of LIM and COM, with 47% of cases being negative. For 500 screens (accounting for 655 individual discrepant findings), at least one discrepancy was noted between LIM and COM. Of these, 399 cases demonstrated at least one finding with COM, but not with LIM ("false-negative" LIM). Topical anesthetics (including cocaine and cocaethylene), antiepileptics, and sympathomimetic amines accounted for 65% of findings. In contrast, 147 cases showed a finding with LIM, but not with COM ("false-positive" LIM), mostly amphetamines. In certain specified clinical circumstances, LIM may be a more cost effective and efficient approach than COM.

Academic Medical Centers↗
PubMed1996

Comprehensive review of cocaethylene and cocaine concentrations in patients.

Cocaethylene (CE) and cocaine (COC) concentrations were reviewed for 41 patients studied by this laboratory and found to have measurable CE in plasma. In 17 instances, urine concentrations of CE and COC were also measured. In 15 cases other drugs in addition to COC and ethanol (ETOH) were detected. Thirty-three cases involved trauma. For the entire series, ages ranged from 19 to 48 years (mean 31 years) with men accounting for 36 cases. Mean concentrations were as follows: plasma CE, 353 nmol/L (range 16.1-1,959); plasma COC, 386 nmol/L (range no measurable amount-1,455); and whole-blood ETOH, 36.5 mmol/L (range no measurable amount-110.9). The ratio CE:COC in plasma ranged 0.1 to 4.7 (mean 1.3). Concentrations of ETOH in whole blood showed significant negative correlation with plasma COC (r = -0.425, P < .01). In addition, plasma CE concentrations showed significant correlation with plasma COC (r = 0.422, P < .01). When available, urine concentrations of CE and COC showed significant correlation with their concentrations in plasma (r = 0.821, P < .01; and r = 0.569, P < .05, respectively). As in plasma, urine concentrations of CE showed significant correlation with urine COC (r = 0.831, P < .01).

Adult↗
PubMed1996

Cocaine and cocaethylene binding to human tissues: a preliminary study.

The tissue binding of cocaine (COC) and cocaethylene (CE) was investigated by equilibrium dialysis of homogenates of whole human tissue supplemented with either COC or CE at concentrations of 10 and 50 microM for each drug. Concentrations of COC and CE were measured by high-pressure liquid chromatography. Kidney bound COC predominantly whereas serum bound it the least (about one tenth as much). In contrast, for CE, most binding was noted to brain with the least to serum (about one twentieth as much). Heart, placenta, and liver showed intermediate binding overall. The binding of COC and CE to these tissues may be important in understanding specific target-organ activity of both compounds.

Adult↗
PubMed1995

Cocaine and cocaethylene binding in human serum.

The binding of cocaine (COC) and cocaethylene (CE) in human serum was studied by equilibrium dialysis. Scatchard analysis suggested a high-affinity binder (Ka, 2.56 x 10(4)L/mol; Bo, 7.38 x 10(-5) mol/L) and a low-affinity binder (Ka, 4.47 x 10(3)L/mol; Bo, 2.77 x 10(-4) mol/L) for COC. Two high-affinity binders (Ka, 5.21 x 10(4) L/mol; Bo, 2.54 x 10(-5) mol/L; and Ka, 4.32 x 10(4) L/mol; Bo, 2.43 x 10(-5) mol/L) were discernible for CE. For both compounds additional, very-low-affinity, high-capacity (nonspecific) binding was also seen. Supplementation of serum with specific proteins suggested that the high-affinity binding was due to alpha-1-acid glycoprotein, whereas the low-affinity binding was due to albumin, inasmuch as such supplementation increased the ratio of bound to free drug for both COC and CE.

Chromatography, High Pressure Liquid↗
PubMed1994

Thin-layer chromatographic detection of cocaethylene in human urine.

A thin-layer chromatographic method was developed for the detection of cocaethylene and cocaine in human urine. Following a standard solid-phase extraction of urine buffered to pH 9.3, the concentrated extract was chromatographed in a solvent consisting of hexane:toluene:diethylamine (65:20:5 mL). Both cocaethylene and cocaine were visualized with iodoplatinate spray. Exclusive of the type of extraction used, the detection limit itself was 16 nmol (5 micrograms) for either compound. The method was applied to urine samples of 13 patients who had ingested cocaine with ethanol. Statistically significant correlations were noted between the intensity of the urine thin-layer chromatographic detection and the measured urine concentrations of cocaethylene and cocaine. The plasma and urine concentrations of both drugs also showed statistically significant correlations. Incorporation of the proposed procedure into commonly used clinical laboratory methodology is described.

Adult↗
PubMed1993

Plasma cocaethylene concentrations in patients treated in the emergency room or trauma unit.

Cocaethylene and cocaine concentrations were measured by high-pressure liquid chromatography in the plasma of 18 patients whose corresponding blood demonstrated ethanol and whose urine contained either benzoylecgonine and/or cocaine on screening for illicit drug use. Although sixteen patients had suffered trauma, only 15 were admitted to the trauma unit. Three patients were seen only in the emergency room. Both cocaethylene and cocaine were detected together in the plasma of 10 patients and not all in 5 patients. In two patients, cocaine was found without cocaethylene, and in one patient cocaethylene was present without cocaine. For the entire series, cocaine concentrations showed significant correlation with those of cocaethylene. Plasma cocaethylene concentrations varied and were as high as 784 nmol/L (249 micrograms/L), and those of cocaine were as high as 1,455 nmol/L (441 micrograms/L). Before this study, published measurements of cocaethylene have been limited almost exclusively to postmortem specimens.

Adult↗
PubMed1992

Interaction of tricyclic antidepressants with cholestyramine in vitro.

The adsorption of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline onto cholestyramine was demonstrated in vitro with use of 1.2 mol/L HCl at 37 degrees C to simulate gastric fluid. Binding to cholestyramine was approximately 80% for each of the tricyclic antidepressants, and this was about the same degree of binding noted with a nonpharmaceutical, non-ionic resin widely used in the diagnostic toxicology laboratory (Amberlite XAD-2). In contrast, five other non-antidepressants (acetaminophen, chlordiazepoxide, procainamide, quinidine, and theophylline) showed only minimal binding to cholestyramine under these conditions. Activated charcoal completely bound all drugs studied. These findings suggest that cholestyramine should be used with caution in patients receiving tricyclic antidepressants. They also suggest that cholestyramine may be a potentially useful adjunctive therapy in treatment of overdose with the tricyclic antidepressants.

Adsorption↗
PubMed1992

Effect of pH changes and ethanol on the binding of tricyclic antidepressants to cholestyramine in simulated gastric fluid.

Tricyclic antidepressants have previously been shown by this laboratory to bind significantly (greater than 80%) to cholestyramine in 1.2 mol/L HCl, used to simulate gastric fluid. This finding has important implications for individuals using tricyclic and cholestyramine concurrently, and it may also have potential therapeutic implications in the treatment of tricyclic overdose. In the present study the effects of pH changes and ethanol on this binding were evaluated. Percent binding of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline decreased from 75-90% (pH 1.0) to 35-50% (pH 4.0). Beyond pH 4.0, however, the binding of each antidepressant increased up to 60-75% at pH 6.5. In contrast, ethanol consistently reduced the percent binding of each antidepressant to cholestyramine in 1.2 mol/L HCl until, in the presence of pure ethanol, the binding ranged from 0% (nortriptyline) to only 32% (doxepin). These findings are important since pH varies widely within the gastrointestinal tract and since ethanol may be co-ingested with cholestyramine and antidepressants.

Antidepressive Agents, Tricyclic↗
PubMed1990

Detection of isopropanol in acetonemic patients not exposed to isopropanol.

Isopropanol has been identified in five acetonemic patients not exposed to this compound. Serum concentrations ranged up to 297 mg/L for IPA and up to 321 mg/L for acetone. Concentration ratios (isopropanol:acetone) ranged up to 5.12. All five patients had Type I diabetes mellitus and were insulin-dependent. At the time isopropanol was detected each patient was hyperglycemic, and four patients were acidotic. These findings tend to corroborate clinically some earlier autopsy reports that acetone may be converted to isopropanol in physiological conditions in which reduced nicotinamide adenine dinucleotide is elevated. The conversion of acetone to isopropanol in vivo has significant clinical and forensic toxicological implications.

1-Propanol↗