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At least 19 recordsLinked to original sources
PubMed1975

Drug interactions: the effects of alcohol and meprobamate applied singly and jointly in human subjects. IV. The concentrations of alcohol and meprobamate in the blood.

The absorption and elimination of alcohol and meprobamate from the blood during Experiments IV (E-IV) and V (E-V) of Carpenter et al. [J. Stud. Alc., Suppl. No. 7, pp. 54-139, 1975] were studied by means of mathematical models representing the relation between doses, concentration in the blood and time elapsing since drug ingestion. The blood concentrations of samples taken 2 and 5.5 hr after beginning to drink in E-IV and 1, 1.5, 2, 2.5, 3.5 and 4.5 hr in E-V were analyzed. The presence of meprobamate did not affect blood alcohol concentration (BAC) in either experiment. At 2 hr the mean BACS after 0.25, 0.50, 0.75 and 1.00 g of alcohol per kg were 6.8, 20.9, 37.7 and 53.7 mg per 100 ml in E-IV; 5.0, 34.1, 42.0 and 72.0 mg per 100 ml in E-V; and 8.1, 32.6, 41.3 and 71.3 mg per 100 ml when calculated by regression from E-V data. The calculated elimination rate of the 2 highest doses of alcohol in E-IV was 6.0 and 7.1 mg per 100 ml per hr; in E-V the mean calculated rates after 0.25-0.75 and after 1.00 g of alcohol per kg were 6.6 and 11.0 mg per 100 ml per hr. The blood meprobamate concentrations (BMC) in E-IV were not affected by alcohol. In E-V, 2.5 and 5.5 hr after meprobamate administration, the combination of 28 mg of meprobamate per kg and 0.75 g of alcohol per kg resulted in significantly lower BMC (7.83 and 12.63 mug per 100 ml) than after same dose of meprobamate with the other doses of alcohol (14.23 and 20.02 mug per 100 ml). The differences between these results and the findings of Carpenter et al. are discussed.

Dose-Response Relationship, Drug↗
PubMed1975

Drug interactions: the effects of alcohol and meprobamate applied singly and jointly in human subjects. III. The concentrations of alcohol and meprobamate in the blood and their effects on performance; application of mathematical models.

The relations between the levels of alcohol and meprobamate in the blood and performance on a visual-motor coordination tracking task were analyzed by a general system of mathematical models, using data from Experiment V by Carpenter et al. [J. Stud. Alc., Suppl. No. 7, pp. 54-139, 1975]. The derivation of the models is described. In general, the relationship between blood alcohol concentration (BAC) and performance was nonmonotonic: best performance occurred at BACS of 10 to 20 mg per 100 ml. The relationship between meprobamate concentration (BMC) and performance was monotonic: performance deteriorated with increasing BMC. The results of the reaction latency measure, howevr, showed no consistent relationship with BAC or BMC. The action of alcohol can be represented by a model which involves 2 distinct sites of action; that of meprobamate, 1 site. It could not be determined whether the site of action of meprobamate is distinct from those of alcohol because the blood levels of the drugs were not high enough. The implications of the results are discussed, with particular reference to the quantitative description of the joint action of drugs and the design of future experiments.

Drug Combinations↗
PubMed1975

Drug interactions: the effects of alcohol and meprobamate applied singly and jointly in human subjects. II. Five experiments.

Five experiments were conducted to study the effects of alcohol and meprobamate, administered singly and in combination, at doses up to 1.20 g of alcohol per kg of body weight and up to 30 mg of meprobamate per kg. Most of the 158 men were of college age (range, 21-49). In all experiments it appeared to the subjects that both drugs were administered, alcohol as a 25% solution in orange juice and meprobamate as 10 tablets. One hour after the men took the meprobamate they had 1 hr to drink the beverage. Before and at 1/2 hr intervals after administration of the drugs blood samples were taken and behavioral response measured by means of a visual-motor coordination tracking task (Stressalyzer). An experimental session lasted 6 hr. In Experiment I (E-I) each of 12 men was tested on 2 days, after 0, 1.00 or 1.20 g of alcohol per kg and 0 or 25 mg of meprobamate per kg. In Experiment II (E-II) 56 men were tested (8 per group) after 0, 5, 10, 15, 20, 25 or 30 mg of meprobamate per kg and alcohol placebo. In Experiment III (E-III) 40 men were tested (8 per group) after 0, 0.25, 0.50, 0.75, or 1.00 g of alcohol per kg and meprobamate placebo. In Experiment IV (E-IV) 25 men (5 per group) received meprobamate 3 times a day (total daily dosage, 0, 7, 14, 21 or 28 mg per kg) for 12 days. On days 8 to 12 all subjects drank alcohol, as in E-III. In Experiment V (E-V) 25 subjects (5 per group) were tested on 5 days, drinking each day the same doses of alcohol as in E-III and all received the same doses of meprobamate as in E-IV.

Adult↗
PubMed1977

Use of hemodialysis in meprobamate overdosage.

A case of meprobamate overdosage successfully treated with hemodialysis is described. The patient was admitted 4 hours after an overdosage of meprobamate (30-40 g) deeply unconscious, hypotensive, in respiratory failure and with a serum meprobamate level of 50 mg/100 ml. Hemodialysis was instituted using a Gambro parallel flow dialyzer and a portable re-circulating dialyzate delivery system (Redy, CCi Life Systems). Meprobamate removal with hemodialysis was 672+/-167 mg/hr with a corresponding clearance of 61.97+/-9.9 ml/min. Drug removal with forced diuresis was 177+/-23.4 mg/hr. Metabolic degradation of the drug was approximately 482 mg/hr with a plasma disappearance rate of 5.2%/hr. No drug could be detected in the dialyzate fluid after its passage through the Redy re-circulating dialyzate system. Because of the rapidity of metabolic degradation of meprobamate, we feel that hemodialysis should be reserved for severe clinical intoxication and either compromised normal excretory routes or progressive clinical deterioration.

Female↗
PubMed1975

Drug interactions: the effect of alcohol and meprobamate applied singly and jointly in human subjects. V. Summary and conclusions.

The design, analysis and conclusions of the series of experiments by Carpenter et al., Ashford and Cobby, and Cobby and Ashford [J. Stud. Alc., Suppl. No. 7, pp. 54-176, 1975] are reviewed. Mathematical models of the joint action of drugs were developed and data obtained to test the models by studying the action of alcohol and meprobamate singly and in combination in human subjects. The data proved to be too limited in the range of drug concentrations in the blood necessary to identify the single most appropriate model. Carpenter et al. analyzed the data by analysis of variance, which involves assumptions about the structure of the observation and the form of the distribution of the error terms. The analyses of Ashford and Cobby and Cobby and Ashford used the mathematical models, which represented pharmacological and physiological actions of the drugs. The majority of the results of the two analyses agreed; however in Experiment V Carpenter et al. combined drugs, doses and blood samples in one analysis anf found a significant influence of meprobamate dose on blood alcohol concentration (BAC) and homogeneous error terms. Cobby and Ashford analyzed absorption and elimination phases of each alcohol dose separately and found no influence of meprobamate on BAC and significant heterogeneity in the residual error terms. Both sets of analyses found a complex interaction between the pattern of abosorption and elimination of meprobamate and dose of alcohol. Carpenter et al. related the results of behavioral measures to drug doses, Ashford and Cobby to the concentrations of the drugs in the blood. Theoretically the models can analyze the pattern of behavioral results at each combination of doses but the data available were insufficient for the purpose. The modifications in experimental design and analytical techniques necessary to continue research in developing mathematical models are discussed.

Behavior↗
PubMed1977

Meprobamate overdosage: a continuing problem.

Meprobamate was implicated in 50 (6.5%) of 773 admissions to Massachusetts General Hospital due to psychotropic drug overdosage between 1962 and 1975. Estimated doses ingested reached as high as 40 gm. Serious intoxication was common. In 25 cases deep coma (grade 3 or 4) was reached; 23 patients became hypotensive, and 16 required assisted ventilation. Two patients died, one of whom ingested an estimated 12 to 20 gm of meprobamate apparently with no other drugs. The findings indicate that overdosage with meprobamate, even when taken alone, produces intoxication that is often serious and sometimes fatal. Although meprobamate is a relatively inexpensive anti-anxiety agent, its questionable efficacy and the potential for life-threatening intoxication are important drawbacks to the clinical use of this drug.

Adolescent↗
PubMed1976

The influence of meprobamate on heart rate in the conscious dog.

The effects of meprobamate on heart rate in the unanesthetized dog were compared under two experimental conditions: (1) In the animal equipped with a telemetry device, in which the heart rate was on average 70/min over a 24 hour period, i.v. injection of 20 mg/kg of meprobamate tended to increase heart rate, a dose of 50 mg/kg provoking a significant tachycardia; (2) In the untrained dog restrained on a table, in which the heart rate ranged from 100 to 110/min, i.v. doses of 20 and 30 mg/kg of meprobamate did not lower heart rate, notwithstanding a significant sedative effect whereas a dose of 50 mg/kg provoked tachycardia; atropine-induced cardio-acceleration was not influenced by these doses of meprobamate.

Animals↗
PubMedDate not supplied

Determination of meprobamate in pharmaceutical dosage forms also containing carbromal by liquid chromatography and indirect photometric detection.

In a pharmaceutical form also containing carbromal, meprobamate could not be quantified selectively by classical methods described in pharmacopoeias due to a significant interference from carbromal. Consequently, reversed-phase HPLC methods have been developed to separate the two active ingredients using indirect photometric detection to visualize and determine meprobamate which has very poor chromophoric properties. Different parameters influencing the sensitivity of the indirect response, such as the nature of the highly absorbing compound added to the mobile phase (the marker) as well as the methanol content and the pH of this phase, have been studied. Two chromatographic systems containing benzoic acid or cinnamic acid as the marker, have been optimized and validated. Good linearity and reproducibility have been obtained with both systems but the cinnamic acid method has the advantage that meprobamate and carbromal can be determined simultaneously at 273 nm.

Benzoates↗
PubMed1976

Subjective and physiologic effects of morphine, pentobarbital, and meprobamate.

These studies extend previous observations on the effects of pentobarbital on subjective states and postrotational nystagmus in postaddict subjects. Pentobarbital (150 mg) induced a degree of liking and an elevation of the morphine-benzedrine group (MBG) scale score equivalent to 24 mg of morphine. The effects of pentobarbital and meprobamate on postrotational nystagmus were studied using electro-oculography. Both drugs increased the frequency and prolonged the duration of postrotational nystagmus in a dose-related manner. Meprobamate was about 1/15 as potent as pentobarbital in enhancing postrotational nystagmus and producing signs of sedation.

Electrooculography↗
PubMed1978

Relative bioavailability of meprobamate tablets in humans.

The relative bioavailability of 400-mg meprobamate tablets manufactured by 11 different firms was evaluated in two groups of healthy male subjects. Each group of six subjects received a reference standard product and five test products given at 1-week intervals. Plasma meprobamate concentrations at 1, 2, 3, 4, 6, 8, 10, 24, and 32 hr after dosing were determined using a GLC assay. Analysis of variance of the plasma level--time profiles revealed no statistically significant differences between any of the products in terms of plasma levels at the various sample times, time of peak plasma level, peak plasma level, and area under the plasma level--time curve. It was concluded that the 11 400-mg products could be considered bioequivalent.

Adult↗
PubMed1978

Clearance of meprobamate by hemoperfusion over columns of charcoal and Amberlite resin. Studies in a patient.

Perfusion of the blood of a patient with toxic levels of meprobamate through an activated charcoal cartridge resulted in efficient early clearance of the drug, then a decline in extraction. Perfusion through a resin column resulted in total drug extraction without a decline in clearance over four hours. Both procedures were stable with minimal disturbance in hematological values or blood chemistries. This is the first report of in vivo hemoperfusion over resin for meprobamate poisoning. The efficacy and safety of the procedure need emphasis.

Adolescent↗
PubMed1977

Severe meprobamate poisoning: successful treatment with haemoperfusion.

Charcoal haemoperfusion used to treat a 56-year-old woman who had taken a very large overdose of meprobamate was followed by fully recovery. The plasma clearance of meprobamate was 153 ml/min and this compares favourably with values obtained for haemodialysis. The indications for haemoperfusion are reviewed.

Charcoal↗
PubMed1975

The effects of three benzodiazepines and of meprobamate on the action of smooth muscle stimulants on the guinea-pig ileum.

The benzodiazepines chlorodiazepoxide, diazepam and flurazepam and meprobamate depress the response of the guinea-pig ileum to acetylcholine, histamine and 5-hydroxytryptamine. As compared to the benzodiazepines the action of meprobamate is very weak. Chlorodiazepoxide has a weaker anti-acetylcholine activity than diazepam and flurazepam. On the other hand chlorodiazepoxide possesses a realtively strong anti-histamine activity. The three benzodiazeptines tested are about equally effective in reducing the contraction of the guinea-pig ileum caused by 5-hydroxytryptamine. The potency of diazepam and flurazepam in blocking the effect of the three smooth muscle stimulants appears to be rather similar.

Acetylcholine↗
PubMed1977

Rapid near IR spectrophotometric determination of meprobamate in pharmaceutical preparations.

A rapid near IR spectrophotometric method was developed for determining meprobamate in tablets, sustained-release capsules, suspensions, and injectables. The absorbance of a chloroform solution of the drug is obtained at about 1.96 mum for quantitation. Assay of nine commercial products from four different manufacturers gave results ranging from 97 to 104% of label claim. Coefficients of variation of 0.7 and 1.3% were obtained on the tablets and a sustained-release product, respectively.

Capsules↗
PubMed1992

Gas chromatographic determination of meprobamate in serum or plasma after solid-phase extraction.

This gas chromatographic technique of determining meprobamate is based on a solid-phase extraction permitting a time reduction of the analysis and improving sensitivity. Quantification is realized on 500 microliters of plasma. The method uses etidocaine as internal standard and does not require derivatization. Thus it is simple, rapid, sensitive and applicable in forensic and clinical toxicological laboratories.

Chromatography, Gas↗
PubMed1975

Antenatal exposure to meprobamate and chlordiazepoxide in relation to malformations, mental development, and childhood mortality.

In a follow-up study of 50,282 pregnancies (lasting at least five lunar months) and the offspring, malformations identified before the first birthday, or at death before the fourth birthday, were identified in 3248 children (6.5 per cent). A total of 1870 children exposed in utero to meprobamate or chlordiazepoxide were compared with 48,412 children who were not. No significant differences were found either overall or in specific outcomes; rates were also similar when exposures occurred during the first trimester or at other times during pregnancy. Deaths (stillbirth to the fourth birthday) occurred in 2227 children (4.4 per cent), and there was no evidence that antenatal exposure to either drug increased the death rate. Finally, as judged by mental and motor scores at the age of eight months, and intelligence quotient scores at four years, there was no evidence that the drugs cause brain damage.

Abnormalities, Drug-Induced↗
PubMed1978

The use of a kymograph in a comparative trial of flunitrazepam and meprobamate in elderly patients.

A double-blind crossover trial was carried out in 31 hospitalized elderly patients receiving night-time sedation to compare the effects of flunitrazepam (0.5 mg) and meprobamate (200 mg). After 1 week on placebo, patients received 1-week's treatment with each drug in random order. Quality of sleep was assessed by a nurse at hourly intervals over 8 hours each night. In 11 patients, the results were compared with those from kymographic recordings measuring patient restlessness (motility index). No statistically significant difference was found between the two active drug treatments, and there was a close correlation between the two methods of assessment. It is suggested that the kymograph may well be a useful and economic method of evaluating the effectiveness of hypnotics.

Aged↗