Search PubMed⌕ Search

Biomedical subjects

N L Benowitz

Publications and source records attributed to N L Benowitz.

At least 235 records · Page 13Linked to original sources
PubMed1983

How a cigarette is smoked determines blood nicotine levels.

Indirect evidence suggests that smoking low-tar and nicotine cigarettes does not necessarily reduce exposure to these substances. Puff volume, duration and number, interpuff interval, and volume and duration of inhalation were measured while 11 subjects smoked two or four tobacco cigarettes. Nicotine blood levels and breath CO were measured before and after smoking. The machine-determined nicotine yields of the cigarettes correlated (r = 0.52) with the increase in nicotine blood levels after smoking but, when individual differences in smoking behavior were taken into account along with the nicotine yield, there was a stronger correlation with nicotine blood levels (r = 0.84 to 0.93).

Breath Tests↗
PubMed1983

Cotinine disposition and effects.

Cotinine is the major metabolite of nicotine in man. We studied cotinine disposition kinetics in 28 healthy habitual cigarette smokers. Eight subjects received cotinine fumarate, 4 micrograms base/kg/min IV for 60 min. Mean (+/- SD) metabolic clearance was 60 +/- 12 ml/min and mean renal clearance was 12 +/- 5 ml/min, averaging 17% of total clearance. Steady-state volume of distribution was slightly greater than body weight (mean 88 +/- 17 l). Terminal t 1/2 averaged 15.8 +/- 4.0 hr in these eight subjects and 19.7 +/- 6.5 hr in another 12 subjects who abstained from smoking for 3 days. The effect of urinary acidification and alkalinization on renal clearance of cotinine during cigarette smoking was studied in another group of eight subjects. Compared with baseline (mean urinary pH 5.8, renal clearance 12.3 +/- 5.9 ml/min), renal clearance was increased about 50% by urinary acidification (pH 4.4, clearance 18.6 +/- 10 ml/min), but it was not affected by alkalinization (pH 6.7, clearance 14.0 +/- 10.4 ml/min). Infusion of cotinine to blood concentrations seen in moderately heavy smokers had no effect on heart rate, blood pressure, or skin temperature, measures that are sensitive to effects of nicotine. No spontaneous subjective effects were reported. We conclude that, at levels to which cigarette smokers are generally exposed, cotinine exerts no cardiovascular activity and weak, if any, psychologic activity.

Adult↗
PubMed1983

The use of biologic fluid samples in assessing tobacco smoke consumption.

In summary, the source, absorption, metabolism, and disposition kinetics of several compounds that are potential markers of tobacco smoke consumption have been reviewed. Kinetic considerations have been applied to discuss specificity and sensitivity of various compounds as markers of cigarette smoking status, usefulness as quantitative indicators of tobacco smoke consumption, and optimal time for sample collection. One cannot, however, escape the conclusion that selection of a biochemical test must be linked to the hypothesis being tested. If only smoking versus nonsmoking is being assessed, then carbon monoxide and/or thiocyanate are inexpensive measurements that provide adequate information. If self-administration of nicotine or toxic effects potentially related to nicotine exposure are being studied, then measurements of nicotine exposure and consumption are required. Measurement of blood concentration of nicotine per se is necessary to document nicotine exposure; blood concentration of cotinine may be a better measure of daily nicotine consumption. To study potentially carcinogenic effects of tobacco smoke, specific measurements of carcinogen consumption must be developed and validated.

Carbon Monoxide↗
PubMed1982

Gas chromatographic analysis of meperidine and normeperidine: determination in blood after a single dose of meperidine.

A method is described for the determination of meperidine and its pharmacologically active metabolite, normeperidine, in blood, plasma, and urine using gas chromatography with nitrogen-phosphorus detection. Structural analogs of both meperidine and normeperidine were used as internal standards. Unlike previously reported assays, this procedure was sensitive and convenient enough for use in pharmacokinetic studies of both meperidine and normeperidine following single doses of meperidine. The assay was sensitive to 5 ng of meperidine/ml and 2.5 ng of normeperidine/ml extracted from a 1-ml biological sample. The between-assay coefficients of variation at these concentrations were 9.4 and 10.4%, respectively.

Adult↗
PubMed1982

Circadian blood nicotine concentrations during cigarette smoking.

To estimate daily nicotine consumption from the smoking of cigarettes delivering different amounts of nicotine, we studied 12 healthy subjects who smoked 30 cigarettes a day of their usual brand (x = 1.2 mg nicotine) or high- (2.5 mg) or low-nicotine (0.4 mg) research cigarettes. Blood nicotine and carboxyhemoglobin concentrations were measured every 2 hr. Nicotine consumption was estimated by the 24-hr area under the blood concentration-time curve (AUC) and compared across smoking conditions. There was considerable interindividual variation in the nicotine AUC among subjects smoking research cigarettes or while smoking usual brands, even when the latter were normalized on the basis of machine-predicted nicotine delivery. Most subjects smoked the high-nicotine research cigarettes less intensively so that nicotine levels were only modestly higher after smoking high-nicotine cigarettes than after usual brands. Low-nicotine research cigarettes were not smoked more intensively than usual brands and blood nicotine levels were substantially lower than those after smoking a usual brand. Nicotine consumption while smoking usual brands correlated strongly with consumption while smoking high- (r = 0.91) and low-nicotine (r = 0.85) research cigarettes. Circadian studies of blood concentration of nicotine while smoking cigarettes provided a direct estimate of the level of nicotine in the body throughout the day. Results confirm observations by others that levels of nicotine in the body vary widely among individuals even when smoking the same number of identical cigarettes. Thus, neither number of cigarettes smoked nor smoking-machine delivery predict daily nicotine exposure very well.

Adult↗
PubMed1982

Increased brain uptake of lidocaine during bicuculline-induced status epilepticus in rats.

Following rapid IV injection (0.1 mg per kilogram) lidocaine HCl concentrations were measured in the blood and brain of paralyzed, ventilated rats during bicuculline-induced status epilepticus and in identically prepared controls. The concentration of lidocaine in blood and brain was consistently higher in convulsing than in nonconvulsing rats. At 1 minute, increased brain lidocaine reflected elevated blood concentrations; increased brain and blood partitioning after 1 minute is responsible for subsequent increases in brain lidocaine uptake. The therapeutic index of lidocaine is low; the concentration of lidocaine is increased in the convulsing brain. Our data suggest that conventional lidocaine doses may perpetuate rather than control refractory convulsions.

Animals↗
PubMed1981

Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects.

Plasma concentrations and urinary excretion of meperidine and its metabolite normeperidine were determined after intravenous and oral administration to 11 men; five men had hepatic cirrhosis and six were normal. Systemic clearance of meperidine was smaller and bioavailability and half-life greater in the cirrhotic patients than in the normal subjects. Plasma concentrations and 24-hr urinary excretion of normeperidine was lower and persistence of normeperidine in plasma longer in the patients with cirrhosis. The route of administration did not alter the fraction of normeperidine generated from meperidine. The results suggest that in patients requiring repeated meperidine dosage the drug should be taken parenterally rather than orally to allow maximal analgesia and minimal formation of normeperidine. Patients with cirrhosis may be relatively protected from normeperidine toxicity because of impaired formation, but the risk of cumulative toxicity may be greater than in normal subjects because of slower elimination of the metabolite and greater sensitivity to the effects of narcotics on the central nervous system.

Administration, Oral↗
PubMed1981

Plasma nicotine and cotinine concentrations in habitual smokeless tobacco users.

Plasma nicotine and cotinine levels were measured in habitual users of smokeless tobacco. The subjects were 12 male college students who regularly used smokeless tobacco (11 dipped snuff and one chewed tobacco) and did not smoke cigarettes. Subjects abstained from tobacco use overnight and blood was drawn at 8 A.M. and again after a single day of ad libitum consumption of their own tobacco product. Subjects recorded the times at which tobacco was used and the remainder product was weighed. Plasma samples were analyzed by both gas-liquid chromatography (GLC) and radioimmunoassay (RIA) techniques. Subjects consumed about one third of a can of moist ground snuff (10.8 gm) in eight dips spaced throughout the day. Nicotine absorption was observed and an increase in mean plasma concentration fro 2.9 ng/ml after overnight abstinence to 21.6 ng/ml after 6 to 8 hr ad libitum consumption was recorded. Plasma cotinine concentrations rose from a morning mean of 137.3 ng/ml to an afternoon mean of 197.2 ng/ml, concentrations that are typical of those reached in regular cigarette smokers. Subjects fell into two subgroups by post hoc analysis: two-thirds absorbed substantial amounts of nicotine and one-third appeared to have almost no absorption. Subjective effects of tobacco use were not marked; there was little perception of physiologic changes, stimulation, or feelings of relaxation/satisfaction. Results are discussed in terms of pharmacologic effects, comparison of results from GLC and RIA methodologies, and implications for health behaviors.

Absorption↗
PubMed1981

Acute vasodilator therapy increases renal clearance of digoxin in patients with congestive heart failure.

We studied the effect of vasodilator therapy on renal digoxin clearance in patients with chronic congestive heart failure. Intravenous administration of nitroprusside or hydralazine to eight patients with severe heart failure produced the expected increase in cardiac output and a decrease in central circulatory pressure. Renal clearance of sodium para-aminohippurate and estimated renal blood flow increased without a change in glomerular filtration rate. Total renal clearance of digoxin increased by 50% during vasodilator therapy. Thus, acute administration of vasodilator increases renal digoxin clearance without changing glomerular filtration rate, suggesting an increase in tubular secretion of digoxin. Long-term vasodilator therapy may alter the maintenance dosage of digoxin required for optimal treatment of patients in congestive heart failure.

Chronic Disease↗
PubMed1981

Phenytoin-induced methadone withdrawal.

Methadone-maintained volunteers experienced moderately severe opiate withdrawal symptoms within 3 or 4 days of beginning phenytoin in therapeutic doses. The area under the methadone plasma concentration-time curve decreased while the ratio of the pyrrolidine-to-metabolite excretion in urine to this area increased significantly. This suggests that phenytoin accelerates methadone metabolism. Methadone dosing adjustments should be anticipated when phenytoin is initiated or discontinued in methadone-maintained patients.

Adult↗
PubMed1981

The cardiovascular and autonomic effects of repeated administration of delta-9-tetrahydrocannabinol to rhesus monkeys.

The cardiovascular effects of repeated dosing with delta-9-tetrahydrocannabinol (THC) were examined in chronically catheterized, conscious rhesus monkeys. THC (0.5 mg/kg) was administered i.v. every 6 hr for 3 weeks. Following the first THC bolus, a tachycardia (peak change, 34 beats/min) and hypotension (peak change, -21 mm Hg systolic blood pressure) sometimes preceded by a transient blood pressure increase were observed. Tolerance developed to the tachycardia and systolic blood pressure increase but not to the blood pressure decrease. Hourly measurement of systolic blood pressure and heart rate during the intervals between injections revealed heart rate decreases to which tolerance developed and blood pressure decreases which were sustained throughout the course of TCH dosing. Urinary catecholamine excretion increased during the 1st week of dosing and subsequently returned toward base-line levels. Control of basal heart rate and reflex heart rate changes was examined using autonomic agonists and antagonists. Heart rate decreases after beta adrenergic blockage (sotalol HCl) were attenuated, whereas heart rate increases after cholinergic blockade (atropine methylnitrate increases after cholinergic blockade (atropine methylnitrate) were augmented. Baroreceptor gain, measured as the ratio of heart rate change to systolic blood pressure change in response to phenylephrine, increased. The response of basal heart rate to antagonists and the augmented reflex bradycardia suggest that THC alters autonomic control of the cardiovascular system resulting in parasympathetic dominance. Divergent patterns of development of tolerance to heart rate and blood pressure effects suggest that THC affects heart rate and blood pressure through different mechanisms.

Animals↗
PubMed1980

An abstinence syndrome following chronic administration of delta-9-terahydrocannabinol in rhesus monkeys.

Chaired, chronically catheterized rhesus monkeys were administered IV delta-9-tetrahydrocannabinol (THC), 0.5 mg/kg every 6 h for 3 weeks. Following the first THC injection, the animals appeared heavy-lidded, immobile, and unresponsive to observation. Tolerance developed to these behaviors during the 3 weeks of THC administration, although the animals remained subdued compared to baseline. Following discontinuation of THC, animals showed an increase in gross movement, eye contact, and tooth baring of greater frequency and/or duration than observed before THC. This presumably represents a cannabis abstinence syndrome.

Animals↗
PubMed1980

Metabolic and psychophysiologic studies of cannabidiol-hexobarbital interaction.

Cannabidiol (CBD), 600 mg/day orally for 5 to 12 days, inhibited hexobarbital metabolism in ten subjects. Hexobarbital oral clearance was 36% lower and apparent volume of distribution was 35% smaller, with no change in half-life during CBD. In four subjects who received intravenous and oral hexobarbital, systemic clearance was 36% lower while bioavailability was 10% greater during CBD. Hexobarbital increased fatigue and tremor, impaired eye-tracking performance, and altered the electroencephalogram. Hexobarbital effects were not affected by CBD. Inhibition of metabolism of other drugs should be considered when large amounts of CBD are taken or when CBD is used for therapy.

Absorption↗