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Biomedical subjects

C L DeVane

Publications and source records attributed to C L DeVane.

At least 91 records · Page 5Linked to original sources
PubMed1991

Disposition of cocaine in pregnant sheep. I. Pharmacokinetics.

Cocaine abuse by pregnant women is increasingly recognized as causing serious health consequences for mother and newborn. To assess the placental transfer and fetal effects of cocaine, we studied its pharmacokinetics following intravenous administration to the pregnant ewe and fetus. Following bolus doses of 0.5-4.0 mg/kg to ewes, cocaine appeared within 30 s in fetal circulation, with peak concentrations occurring in 4-5 min. The disappearance of cocaine in the fetal plasma paralleled that in maternal plasma, suggesting that a rapid equilibrium of cocaine occurred between maternal and fetal compartments. The mean half-life of cocaine in the fetus across doses (4.4-5.0 min) was similar to that in the ewe (4.0-5.6 min). Plasma clearance of cocaine in the ewe did not appear to vary according to dose. The fetal exposure to cocaine, as indicated by the area under the fetal plasma concentration versus curve, was a linear function of maternal cocaine dose (r = 0.96, p less than 0.01). These results demonstrate rapid placental transfer of cocaine after maternal administration in an animal model and rapid metabolism by mother and fetus.

Animals↗
PubMed1991

Disposition of cocaine in pregnant sheep. II. Physiological responses.

We studied maternal and fetal blood pressure, heart rate, arterial blood gases and fetal behavioral state alterations in response to maternally administered cocaine hydrochloride in 11 pregnant sheep. Cocaine administration to the ewe caused a dose-dependent increase in maternal blood pressure and heart rate and in fetal blood pressure, and a decrease in fetal arterial oxygen tension. In the ewe, blood pressure changes corresponded linearly to dose administered (r = 0.88, p less than 0.001). Blood pressure changes were correlated to peak plasma cocaine concentration in the ewe (r = 0.52, p less than 0.01) and in the fetus (r = 0.43, p = 0.05). In addition, in 7 of 8 fetuses which had entered rapid eye movement (REM) sleep within 5 min of maternal cocaine administration, REM sleep was abruptly terminated either by the cocaine, fetal hypoxia or some other nonspecific event caused by the maternal cocaine administration. Maternal cocaine administration causes maternal and fetal hemodynamic alterations that have potential adverse effects in pregnancy.

Animals↗
PubMed1990

Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease.

Bupropion hydrochloride is a new monocyclic antidepressant. In humans, its disposition results in the formation of three major metabolites: the morpholinol metabolite, the erythroamino alcohol, and the threoamino alcohol metabolite. Bupropion's disposition was monitored following a single oral 200 mg dose in eight healthy volunteers and eight age- (44.5 +/- 8.4 years) and weight- (77.4 +/- 6.7 kg) matched volunteers with alcoholic liver disease. This latter group is of interest because the incidence of depression is more frequent in alcoholics than in the general population, and the liver is the major route of elimination for cyclic antidepressants. The mean elimination half-life of the morpholinol metabolite was significantly prolonged in subjects with alcoholic liver disease (32.2 +/- 13.5 vs. 21.1 +/- 4.9 hours (p less than 0.05), while the differences in bupropion (17.3 +/- 8.6 hours vs. 16.5 +/- 10.4 hours for healthy subjects and subjects with alcoholic liver disease, respectively), erythroamino alcohol (26.1 +/- 13.3 hours vs. 29.8 +/- 6.9 hours for healthy subjects and subjects with alcoholic liver disease, respectively), and threoamino alcohol (25.5 +/- 8.6 hours vs. 23.4 +/- 10.7 hours for healthy subjects and subjects with alcoholic liver disease, respectively) were minimal. Mean area under the plasma concentration time curves for bupropion and metabolites were increased in subjects with alcoholic liver disease; however, clear differences between means of these small groups did not emerge, probably due to the increased variability of bupropion pharmacokinetics in these subjects. As a therapeutic agent for the treatment of depression in chronic alcoholics who may consume alcohol in combination with their antidepressant therapy, the lack of sedation with bupropion could be advantageous.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Imipramine treatment of panic disorder during pregnancy.

Two women with panic disorder who continued to be symptomatic during pregnancy were successfully treated with low doses of imipramine. Plasma drug concentrations were lower than usually required for antidepressant response and remained relatively stable during gestation. Each woman delivered a healthy infant with minimal discomfort from panic symptoms during pregnancy. These cases are illustrative of two women who had a need of and benefited from pharmacotherapy for panic disorder during pregnancy.

Adult↗
PubMed1989

Tissue distribution of cocaine in the pregnant rat.

Cocaine hydrochloride was administered by single intraperitoneal (IP) doses to pregnant rats at day 18 or 19 of gestation. Plasma and tissue cocaine and norcocaine concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic analysis of concentration versus time data showed rapid distribution of cocaine and its metabolite to maternal and fetal tissues. The area under the cocaine concentration versus time curve (AUC) in fetus compared to maternal plasma was 3.33. The half-life of cocaine in the maternal plasma and fetus was 46 and 55 minutes, respectively, similar to values reported for cocaine elimination half-life in human plasma. The order of cocaine concentrations was placenta greater than fetal liver greater than maternal heart greater than whole fetus greater than fetal brain greater than maternal brain = maternal plasma. Norcocaine concentrations were usually less than 20% of cocaine concentrations in plasma and tissues. These results support extensive fetal exposure to cocaine following administration to pregnant rodents. Pharmacodynamic studies of cocaine in pregnancy should consider the effects of the drug on the developing fetus.

Animals↗
PubMed1987

Lack of interaction of ranitidine with amitriptyline.

The possibility of an interaction of ranitidine with amitriptyline was assessed by means of amitriptyline and nortriptyline plasma concentration measurements, blood pressure and pulse rate, digit symbol substitution, and visual analogue scales. Ranitidine had no effect on amitriptyline or nortriptyline concentrations. Responses recorded by the digit symbol substitution and visual analogue scale tests correlated with changes in concentrations of amitriptyline and nortriptyline in plasma. No effects on blood pressure or pulse rate were observed. We concluded that there was no effect of ranitidine on amitriptyline kinetics or response in the conditions of our study.

Adult↗
PubMed1987

Monitoring cyclic antidepressants.

Therapeutic drug monitoring of antidepressants can ensure that a reasonable amount of drug reached the circulation, can aid in dosage adjustments for treating endogenous depression, can avoid toxicity, and aid in the diagnosis of drug-induced delirium. This article reviews the justification for antidepressant monitoring, discusses sample collection procedures, and presents guidelines for the interpretation of data.

Aged↗
PubMed1986

The effect of experimentally-induced renal failure on accumulation of bupropion and its major basic metabolites in plasma and brain of guinea pigs.

Dosage regimen adjustments because of poor renal function are often assumed to be unnecessary for extensively metabolized antidepressants. This assumption is being increasingly questioned in recognition of the role of active drug metabolites. The purpose of this study was to assess the steady-state accumulation of the new antidepressant bupropion and its three major basic metabolites in guinea pigs, with and without experimentally-induced renal failure. Two groups of guinea pigs were treated by intraperitoneal (IP) implantation of mini-osmotic pumps containing bupropion hydrochloride. Immediately after surgery, one group of animals received an injection of uranyl nitrate. After 4 days, all animals were sacrificed by decapitation following blood removal by cardiac puncture. Analysis of plasma and brain samples by high performance liquid chromatography (HPLC) for concentrations of bupropion (BUP) and its major basic metabolites, the erythro-amino alcohol (EB), the threo-amino alcohol (TB) and the hydroxy metabolite (HB) revealed greater accumulation of BUP, TB, and HB in plasma and brain of the animals with renal failure compared to controls. No difference was found between groups in the concentrations of the EB metabolite. As the guinea pig shows a BUP and metabolite plasma concentration profile similar to that seen in human studies, these results suggest that further studies of bupropion and its major metabolites are warranted in patients with impaired renal function to assess possible excessive drug and metabolite accumulation.

Animals↗
PubMed1985

Diurnal variation of alpha 1-acid glycoprotein concentration in normal volunteers.

The serum concentration of alpha 1-acid glycoprotein (AAG) was determined hourly for 25 h in male and female volunteers. Subjects were carefully selected to control for age, weight, health status, smoking history, medication use, and, for females, estrus cycle and oral contraceptive use. Studies were performed under conditions closely controlled for sleep, daytime environment, and diet. All mean concentrations were within the range reported as normal, but the deviation around individual means varied from 6.4 to 48.9%. Males had higher mean AAG concentrations than females, 59.9 versus 52.4 mg/dL, but the difference was not statistically significant. Studies which compare changes in AAG concentration or the degree of basic drug protein binding over time within individuals or between groups should consider intrasubject variability in AAG for accurate interpretation of results.

Adult↗
PubMed1985

Cimetidine interaction with amitriptyline.

The interaction of cimetidine with amitriptyline was assessed by means of amitriptyline and nortriptyline plasma concentration measurements, standing blood pressure and pulse rate, digit symbol substitution, and visual analogue scales. Cimetidine increased plasma amitriptyline concentrations and decreased plasma nortriptyline concentrations, apparently by inhibiting presystemic metabolism. The changes in blood pressure, pulse rate and digit symbol substitution correlated with changes in concentrations of amitriptyline in plasma and expected changes based on a dose ranging preliminary experiment. Changes in subjective ratings of effects correlated with changes in nortriptyline concentrations in plasma.

Adult↗