Biomedical subjects

D N Bailey

Publications and source records attributed to D N Bailey.

At least 73 records · Page 4Linked to original sources

PubMedDate not supplied

Propylene glycol as a vehicle for percutaneous absorption of therapeutic agents.

Propylene glycol (PG) was evaluated as a vehicle for the in vivo percutaneous absorption of the hydrochloride salts of desipramine, nortriptyline, procainamide, and N-acetyl-procainamide. Each drug was administered topically to hairless (hr-1/hr-1) mice in water and in aqueous 10% and 50% PG. Mean drug concentrations in blood, brain, heart, liver, and lung were measured by high-pressure liquid chromatography after either two or three hours of topical absorption. The presence of PG generally enhanced the absorption of each drug, and the degree of enhancement appeared to be related to the percentage of PG in the dosing solution.

Acecainide↗

PubMedDate not supplied

Serial plasma concentrations of cocaethylene, cocaine, and ethanol in trauma victims.

Cocaethylene (EC), cocaine (COC), and ethanol (ETOH) concentrations were measured in 46 serial plasma samples from 15 male trauma victims. In all but two patients EC was detected on admission to the hospital. In the remaining two, EC was not detected throughout hospitalization. However, these two patients had the lowest ETOH concentrations in the series (200 and 300 mg/L). Plasma concentrations ranged up to 128 micrograms/L for EC, up to 421 micrograms/L for COC, and up to 5,100 mg/L for ETOH. Ratios of EC to COC concentration (EC/COC) were as high as 4.1. Concentrations of EC showed statistically significant correlation with those of COC (p < 0.01). The plasma half-life (T1/2) of EC was found to be longer than that reported for COC (1 h) and was estimated to be 3.5, 4.5, and 5.5 h in three patients.

Adult↗

PubMedDate not supplied

Studies of cocaethylene (ethylcocaine) formation by human tissues in vitro.

The potential for different human tissues to form cocaethylene (ethylcocaine) (EC) was evaluated by incubation of homogenates of brain, kidney, liver, lung, and placenta in vitro with cocaine (COC) and ethanol. Only liver yielded measurable concentrations of EC over time, accompanied by a decrease in COC concentration. Although mouse kidney has been reported to produce EC in similar experiments, in the present studies human kidney did not. Interestingly, incubation of human liver homogenates with EC and methanol yielded COC, with a concurrent decrease in EC concentration. This suggests that previously described hepatic esterases can catalyze the transesterification of both EC and COC.

Adult↗

PubMedDate not supplied

Cocapropylene (propylcocaine) formation by human liver in vitro.

Formation of cocapropylene (CP), the n-propyl analogue of cocaine, by human liver has been demonstrated for the first time through incubation of whole liver homogenates with cocaine (COC) and n-propanol (PrOH). The formation of CP was noted by 30 min in each case, and it continued throughout the 6-h study period. The concentration of COC declined throughout each incubation. Sodium fluoride was found to inhibit completely the formation of CP. For control purposes, the capability of each liver to generate cocaethylene (CE), the known transesterification product of COC and ethanol (EtOH), was established by separate incubation of the homogenate with COC and EtOH. Concentrations of COC, CP, and CE in the respective homogenates were measured by reversed-phase high-performance liquid chromatography, whereas those of EtOH and PrOH were measured by gas-liquid chromatography.

1-Propanol↗

PubMedDate not supplied

Formation of cocaisopropylene (isopropylcocaine) by human liver in vitro.

The formation of cocaisopropylene (CI), the isopropyl homologue of cocaine (COC), was demonstrated by the incubation of whole human liver homogenates with cocaine hydrochloride and isopropanol. Measurable concentrations of CI were noted within 1 h of incubation. The reaction was completely inhibited by sodium fluoride. As a control on hepatic enzymatic activity, aliquots of the same homogenates were also incubated with COC and ethanol to yield cocaethylene (CE), which was previously demonstrated by this system. Peak concentrations of CI were approximately 0.1-0.2 of those of CE.

1-Propanol↗

PubMedDate not supplied

Cocaethylene (ethylcocaine) detection during toxicological screening of a university medical center patient population.

Cocaethylene (ethylcocaine) (CE) was incorporated into this laboratory's urine toxicological screening protocol more than 1 year ago. During a 1-year period, 451 urine specimens tested positive for benzoylecgonine (BE) and/or cocaine (COC) and/or CE using a combination of thin-layer chromatography with enzyme immunoassay confirmation. CE was detected in 57 urine specimens. Blood ethanol (EtOH) analysis was available for 37 of these cases, and the mean concentration (1320 mg/L) was significantly higher than that found in 117 blood EtOH assays performed for the CE-negative patients (630 mg/L) (p < .01). In two instances, CE was noted in urine in the absence of EtOH in the corresponding blood. Without exception, CE, when present in urine, was always detected with both BE and COC. Most of the time, no other drugs were found. In one instance, CE was present in the urine of a neonate but was not detected in that of its mother. Demographic and analytical findings are presented for both CE-positive and CE-negative cases.

Adolescent↗

PubMedDate not supplied

Relative binding of acetaminophen, lidocaine, phenobarbital, phenytoin, quinidine, and theophylline to human tissues in vitro.

The relative binding of acetaminophen, lidocaine, phenobarbital, phenytoin, quinidine, and theophylline to human tissues in vitro was studied using equilibrium dialysis. Pooled human serum plus homogenates of brain, heart, liver, and placenta were incubated at 4 degrees C with each drug at concentrations of 5 and 10 mmol/L. The percent binding of each drug to each tissue was calculated. Binding of 5% or less was considered to be negligible. By drug, the following relative binding orders were observed for those tissues demonstrating binding: acetaminophen (heart > brain, serum); lidocaine (no appreciable binding observed); phenobarbital (serum only); phenytoin (heart and liver equally; serum not studied); quinidine (serum > liver > brain, placenta); and theophylline (serum > liver). By matrix, serum bound all drugs studied except for lidocaine. Liver bound only phenytoin, quinidine, and theophylline; heart bound only acetaminophen and phenytoin; brain bound only acetaminophen and quinidine; and placenta bound only quinidine.

Acetaminophen↗

PubMedDate not supplied

Cocaine- and cocaethylene-creatinine clearance ratios in humans.

Cocaine (COC)- and cocaethylene (CE)-creatinine clearance ratios (CCR) were determined in five patients. In each case, COC:CCR greatly exceeded CE:CCR, and in four patients the data suggested renal tubular secretion of COC. For all patients, some renal tubular reabsorption of CE was apparent. These findings may be due, at least in part, to the greater hydrophobicity of CE relative to COC and to the lower pKb of CE (8.23) than that of COC (8.60). The pKb of CE was determined by titrimetry and is reported here for the first time. These data may be useful in investigating the pharmacokinetic profiles of COC and CE in humans and may also help to explain the longer plasma half-life of CE relative to that of COC.

Adult↗

PubMedDate not supplied

Relative binding of therapeutic drugs by sera of seven mammalian species.

The relative binding of acetaminophen, lidocaine, phenobarbital, procainamide, quinidine, and theophylline to sera of seven mammalian species was studied. Pooled commercial sera from cow, goat, horse, human, pig, rabbit, and sheep were supplemented with 5 and 10 mM concentrations of each drug. For each serum, each drug, and each drug concentration, equilibrium dialysis was performed in duplicate against phosphate buffer (pH 7.4, 0.1 M, 4 degrees C). Percent drug bound to serum was calculated. Phenobarbital demonstrated more than 20% binding to goat, horse, human, and sheep serum at both 5 and 10 mM concentrations; more than 20% binding to bovine serum at a concentration of 10 mM; and more than 20% binding to pig and rabbit serum at 5 mM. Quinidine (studied only at 5mM concentration) bound more than 20% to cow, goat, horse, human, pig, and rabbit serum. In contrast, procainamide at both the 5 and 10 mM concentrations showed no binding to cow, horse, pig, rabbit, or sheep serum. Acetaminophen (studied only at 5 mM concentration), lidocaine, and theophylline demonstrated less than 20% binding to each serum. Acetaminophen at 5 mM did not bind to human serum, and lidocaine at 10 mM did not bind to horse or pig serum. Although some interspecies variation in drug binding to the seven sera was noted, the overall magnitude of binding of each drug to each serum was, for the most part, similar. Phenobarbital and quinidine showed stronger (> 20%) binding; procainamide showed negligible binding; and acetaminophen, lidocaine, and theophylline demonstrated intermediate (< 20%) binding.

Acetaminophen↗

PubMedDate not supplied

Amitriptyline and procainamide inhibition of cocaine and cocaethylene degradation in human serum in vitro.

Amitriptyline (AMI) and procainamide (PA) have been reported to inhibit the activity of human plasma butyrylcholinesterase, an enzyme important in the metabolic degradation of cocaine (COC) and its ethyl analogue cocaethylene (CE). Because both AMI and PA may be used in the treatment of COC intoxication and abuse, the effect of high pharmacological concentrations of these compounds on the degradation of COC and CE in pooled human serum was studied. AMI (1.8 micromol/L) modestly inhibited the degradation of COC by 4.2% and of CE by 4.0%. PA (42.5 micromol/L) profoundly inhibited degradation of COC by 42.7% and of CE by 47.2%. In contrast, lithium carbonate (1 mmol/L, control) showed no inhibition of degradation of either COC or CE. These results suggest that AMI and PA may prolong the half-life of COC and CE in human serum.

Amitriptyline↗

PubMedDate not supplied

Procainamide inhibition of human hepatic degradation of cocaine and cocaethylene in vitro.

Procainamide (PA), a cardioactive drug, inhibited the degradation of both cocaine (COC) and cocaethylene (CE) when either was incubated in human liver homogenates for 3 h at 37 degrees C. PA appeared to enhance the formation of CE when COC and ethanol (ETOH) were incubated together in liver homogenate. These observations are clinically significant because cardiotoxicity is common after COC abuse and because PA may be administered to individuals who use COC alone and with ETOH.

Aged↗

PubMedDate not supplied

Survey of drug-abuse patterns and toxicology analysis in an emergency-room population.

A retrospective survey of 150 patients who presented to a university hospital emergency room with suspected drug abuse was performed. In 74 instances, biological fluids were submitted to the laboratory for toxicology analysis. Drugs implicated in the clinical history were compared with those actually found by the laboratory in order to evaluate the diagnostic utility of toxicology testing. The laboratory found either some or all of the drugs suspected from the history in 68% of the laboratory-analyzed cases. In an additional 16% the laboratory found none of the implicated drugs but did find other drugs not suggested by the history, and in one of every four cases at least one drug not implicated by history was found. The most frequently involved drugs in this study are identified, and epidemiologic parameters including age, sex, frequency of multiple-drug ingestions, patient disposition, and patient and laboratory-sample arrival times are analyzed.

Adolescent↗

PubMedDate not supplied

Survey of admission toxicology panels in patients with multiple hospitalizations.

Of 1309 different patients with toxicology panels performed on admission to our university medical center during 1978-79, 65 (5.0%) had more than one hospitalization or emergency-room visit. The average patient with multiple admission panels performed during the year was an alert 32-year-old man who presented to the emergency room a mean of 2.2 times, following an episode of suspected drug abuse. The visits were separated by a mean time interval of 2.5 months. An average 1.7 different drugs per patient were found on the admission toxicology screening (usually ethanol, a barbiturate, an opiate, or a phenothiazine). One third of the drugs per patient were positive again on subsequent hospitalizations of the patient. In more than a third of the instances in which repeated drugs were quantitated, the "repeat level" on the subsequent admission was within +/- 17% of that found on the first admission. Laboratory recognition of patients with repetitive admission toxicology screening may facilitate analysis by permitting specific-drug-oriented searches.

Adolescent↗

PubMedDate not supplied

Interpretation of blood and tissue concentrations in fatal self-ingested overdose involving amitriptyline: an update (1978-1979).

Thirty-two cases of fatal self-ingested overdose involving amitriptyline were studied over the two-year period 1978 to 1979. The average decedent was a 44-year-old woman who ingested amitriptyline and at least one other drug (usually ethanol, diazepam, propoxyphene, or codeine). The mean concentrations of amitriptyline and nortriptyline were significantly higher in liver than in myocardium, and they were significantly higher in myocardium than in blood. In addition, concentrations in these tissues showed significant correlation with each other. The mean tissue concentrations of amitriptyline and nortriptyline in this series of overdoses were significantly greater than those in fourteen other decedents whose deaths were not due to drug overdose but involved amitriptyline as an incidental finding. The mean ratio of amitriptyline to nortriptyline in each tissue was also significantly higher in overdose than those in the corresponding tissues of the non-overdose group, suggesting that the former ingestions were more acute. The estimated survival times showed no significant correlation with tissue concentrations of either amitriptyline or nortriptyline.

Adult↗

PubMedDate not supplied

Measurement of phencyclidine in saliva.

Following intraperitoneal injection of phencyclidine in the rat, concentrations ranged from 148 to 1364 ng/mL in saliva (mean +/- SD, 567 +/- 415) and from 196 to 1016 ng/mL in corresponding serum samples (mean +/- SD, 502 +/- 231). Phencyclidine concentrations in saliva showed no significant correlation with those in serum, and saliva concentrations were occasionally higher than serum concentrations. The saliva:serum concentration ratios ranged from 0.4 to 3.0. Since hypersalivation is common in man and animals after phencyclidine ingestion, measurement of the compound in saliva may provide a useful alternative to serum and urine which are not always available for analysis.

Animals↗

PubMedDate not supplied

Methaqualone ingestion: evaluation of present status.

Sixty cases of methaqualone ingestion have been reviewed from 1977 through 1980. Serum methaqualone concentrations, clinical information, and demographic data were studied in order to define the present status of abuse of this drug. The average user was a 27 year-old man who ingested Quaalude plus at least one additional drug (usually a narcotic analgesic, ethanol, a benzodiazepine, or a barbiturate, in that order). He was admitted to the emergency room with a depressed level of consciousness and a serum methaqualone concentration of 5 +/- 3 mg/L (mean +/- SD). Following a brief period of observation and supportive care, he was discharged from the hospital. Serum methaqualone concentrations showed no significant correlation with the physical findings, except that levels greater than or equal to 9 mg/L were always associated with a depressed level of consciousness, whether or not other drugs were present. Despite strict federal controls, methaqualone abuse appears to be a continuing problem, and analysis for this drug should be part of the toxicology screen.

Adolescent↗

PubMedDate not supplied

A study of salicylate and caffeine excretion in the breast milk of two nursing mothers.

Salicylate excretion was studied in the breast milk of a nursing mother (Patient A) taking chronic therapeutic doses of aspirin, and caffeine excretion was monitored in the breast milk of a nursing mother (Patient B) who was a heavy coffee drinker. Salicylate concentrations were maximal in serum at 2.25 hours (10.8 mg/dL) and in milk at 3.00 hours (1.0 mg/dL) following 975 mg of aspirin in Patient A. Caffeine concentrations peaked at 5.50 hours in serum (2.14 micrograms/mL) and at 2.00 hours in milk (1.15 micrograms/mL) during a period of steady coffee drinking by Patient B. Milk:serum concentration ratios ranged up to 0.08 for patient A and up to 0.63 for Patient B, demonstrating that relatively more caffeine than salicylate was excreted into milk. Sodium, potassium, pH, and percent solute remained essentially unchanged in milk samples from both patients throughout the study periods so that changes in the state of hydration of pH of the milk could not be implicated for the observed excretion patterns. More than 25 liters of milk at its peak drug concentration would have to be consumed by the infants of Patients A and B respectively to provide the salicylate content of one aspirin tablet or the caffeine content of an average cup of coffee.

Adult↗

PubMedDate not supplied

The unusual occurrence of 4-aminoantipyrine (4-aminophenazone) in human biological fluids.

During toxicology screening of human biological fluids, 4-aminoantipyrine (4-AAP) was detected in 19 patients and identified by two-dimensional TLC and UV spectrophotometry with whole blood concentrations of 4-AAP ranging from 0.4 to greater than 4.9 mg/dL. Of the 19 patients, 15 had received prior treatment at a Mexican health-care facility before transfer to this medical center. Since 4-AAP is a known metabolite of aminopyrine, it is likely that the patients had ingested this anti-inflammatory, analgesic agent in Mexico; however, the clinical histories in this respect were vague. Recognition of the presence of 4-AAP in biological fluids is important, since the parent drug may produce fatal agranulocytosis and the compound may complicate the detection of other compounds that simultaneously partition into the weak-base fraction in toxicology screening.

Adolescent↗