Disposition of glutethimide in man

Curry, Stephen H.; Riddall, Dieter; Gordon, John S.; Simpson, Pippa; Binns, T. B.; Rondel, R. K.; McMartin, Colin

doi:10.1002/cpt1971125849

Cited by 43 publications

(9 citation statements)

References 7 publications

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“…Limited information is available with respect to the disposition of glutethimide in man following therapeutic doses. Curry et al (1971) showed that the absorption rate of glutethimide tablets was very variable, with peak level times between I and 6h; the range of the elimination half life was.5 to 22h for 6 volunteers, with an average value of 11.6h. Similar values were obtained by Kadar et al (I 974).…”

Section: 9 Glutethimidementioning

confidence: 98%

Clinical Pharmacokinetics of Hypnotics

Breimer

1977

Clinical Pharmacokinetics

115

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The intermittent type of drug action which is desired in hypnotic treatment is fundamentally different from those types of drug treatment where a constant effect is required. Thus, in insomnia, drug action should be restricted to the duration of the night and residual effects should be absent during day-time. During daily administration there should be no accumulation of the drug. These factors taken together, mean that a rapid rate of elimination is of advantage for a hypnotic. In addition, the patient taking a hypnotic expects that sleep is readily obtained and therefore biopharmaceutical factors, especially those promoting a rapid rate of absorption, are crucial for hypnotic drug formulations.Many barbiturates have a relatively long elimination half life, except methohexitone, hexobarbitone and cyclobarbitone. The traditional classification of barbiturates into long-, intermediate-and short-acting compounds bears no relation to the rate of elimination in humans, and for this and other reasons, should be abandoned. Barbiturate salts are rapidly absorbed, in contrast to the free acids. Liver disease tends to decrease the elimination rate of these compounds, whereas renal insufficiency may give rise to accumulation of polar metabolites (e.g. hydroxyamylobarbitone). Methaqualone, too, has a long elimination half life, so that accumulation may occur during daily administration. Absorption of this compound appears to be quite rapid from the formulations investigated.Although the benzodiazepines nitrazepam and ./lurazepam are the most frequently used hypnotics today, information concerning their pharmacokinetics in humans is very limited. The elimination half life of nitrazepam is between 18 and 34 hours, whereas that of unchanged ./lurazepam has not been accurately determined. However, the N-desalkyl metabolite of ./lurazepam, which has pharmacological properties comparable to the parent drug, has an elimination half life of 2 to 4 days. Substantial accumulation of this metabolite occurs during daily administration of ./lurazepam. The active metabolite of chloral hydrate (trichloroethanol) is quite rapidly eliminated (t /f2 = 7 to IOh), whereas another important metabolite (trichloroacetic acid, t 1/2 = 4 to 5 days) gives rise to substantial accumulation during chronic administration. The potential protein binding displacement interaction of this compound with coumarin oral anticoagulants such as warfarin, should always be considered in clinical practice.

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Section: 9 Glutethimidementioning

confidence: 98%

Clinical Pharmacokinetics of Hypnotics

Breimer

1977

Clinical Pharmacokinetics

115

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“…The only reported data of glutethimide passage into human milk [76] allow a M/P ratio of 0.15 to be calculated 8 hours after a single oral 500mg dose. Its elimination halflife varies between 5 and 22 hours.…”

Section: Other Drugsmentioning

confidence: 99%

Excretion of Psychoactive Drugs into Breast Milk

Pons

Rey

Matheson

1994

Clinical Pharmacokinetics

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The postpartum period is a time of great physical and emotional changes. The incidence of psychiatric illness is higher in this period than at any other time in a women's life. Therefore, the question of whether women receiving psychotropic drugs should continue breast feeding is an important one. Drug excretion in breast milk depends mostly on passive diffusion of the unionised unbound drug. Passive diffusion is affected mainly by the drug disposition in lactating mothers, by the physicochemical properties of the molecule and by the protein and lipid contents of breast milk. Indeed, breast milk can be considered as a compartment with bidirectional transfer rather than a reservoir into which drug accumulates. Benzodiazepines are the most prescribed psychotropic drugs. Generally there does not seem to be any contraindication to breast feeding after a single dose, provided the dose administered is relatively low. If higher doses are to be used or long term administration is required, then breast feeding should probably be discontinued, particularly with drugs with a long elimination half-life. On the basis of the average concentration of phenobarbital (phenobarbitone) in milk, breast feeding is not recommended. For glutethimide, breast feeding would appear to be safe for the infant when a single dose is taken occasionally. Zopiclone may also be prescribed on a short term basis to breast feeding mothers. Due to limited available data or to the large amount transferred to milk, administration of phenothiazines and nonphenothiazine tricyclic, butyrophenone, and benzamide antipsychotics to breast feeding mothers cannot be recommended. Breast feeding is not always considered an absolute contraindication to lithium therapy, but the mother should watch for signs of toxicity in her baby. Whether clomipramine should be contraindicated during breast feeding depends on the concentration of active metabolites in breast milk, and this has not yet been determined. It is probably safe for mothers to breast feed while receiving amitriptyline, but before more conclusive recommendations are made more infants should be studied. The available data suggest that the amount of doxepin and its metabolite in breast milk is small. However, the metabolite of doxepin may accumulate in the infant with risk of sedation and respiratory depression: therefore, an alternative antidepressant should be selected for breast feeding mothers.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…It is highly lipid-soluble and its main route of elimination from the body is through hepatic metabolism (Curry, Riddall, Gordon, Simpson, Binns, Rondel & McMartin, 1971). It has been shown to shorten warfarin plasma half life (Corn, 1966), to cause a fall in steady state plasma warfarin levels (MacDonald, Robinson, Sylwester & Jaffe, 1969) and to decrease the hypoprothrombinaemic effect of warfarin (Udall, 1975) by hepatic microsomal enzyme induction.…”

Section: Introduictionmentioning

confidence: 99%

The features of hepatic enzyme induction with glutethimide in man.

Jackson¹,

Homeida²,

Roberts³

1978

Brit J Clinical Pharma

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1 Sequential measurements of D‐glucaric acid excretion were made in six healthy volunteers before, during and after 3 weeks' daily medication with glutethimide 500 mg. 2 There was a rapid rise in D‐glucaric acid excretion within 2 days of starting medication and a rapid decline when it was stopped. 3 Antipyrine clearance and indocyanine green clearance were measured before and at the end of the 3 weeks' medication. 4 There was a 55% increase in antipyrine clearance but no change in indocyanine green clearance. 5 There was no correlation between antipyrine clearance and D‐glucaric acid excretion. 6 Glutethimide causes rapid enzyme induction in man without concomitant rise in hepatic blood flow.

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Disposition of glutethimide in man

Cited by 43 publications

References 7 publications

Clinical Pharmacokinetics of Hypnotics

Clinical Pharmacokinetics of Hypnotics

Excretion of Psychoactive Drugs into Breast Milk

The features of hepatic enzyme induction with glutethimide in man.

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