Plasma Imipramine Level in Syndromes of Depression

Haydu, George G.; Dhrymiotis, Andreas; Quinn, Gertrude P.

doi:10.1176/ajp.119.6.574

Cited by 25 publications

(3 citation statements)

References 1 publication

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“…[ 12) Blood concentrations (of imipramine plus desipramine) in the range of 150 to 250 Ilg/L appear to correlate with improved clinical response. ll31 A recent review f131 found that of 20 studies on imipramine, [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] 60% of studies found a relationship between plasma drug concentration and therapeutic response, and 92% of these studies reported a linear relationship.…”

Section: Imipraminementioning

confidence: 99%

Pharmacokinetic Optimisation of Therapy with Newer Antidepressants

Goodnick

1994

Clinical Pharmacokinetics

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Since the early 1950s, when imipramine was first introduced, a whole series of antidepressants with differences in structures, neurochemical effects and pharmacokinetics have been developed. Structurally or functionally, they have been classified as tricyclic antidepressants (TCAs), tetracyclic antidepressants, monoamine oxidase inhibitors (MAOIs), or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). In addition, there is a series of antidepressants with unique structures. Many of the newer TCAs appear to have shorter half-lives than the standard TCAs (e.g. imipramine), allowing for the possibility of a more rapid response, but requiring the drugs to be given in multiple daily doses, which may reduce patient compliance. The short time to peak plasma concentration (tmax) can also lead to rapid onset of adverse effects. The tetracyclic antidepressants have longer elimination half-lives (t1/2) than the TCAs, but there is only very minimal evidence for a relationship between drug concentrations in the blood and clinical response. The triazolopyridines, like the newer TCAs, show pharmacokinetic evidence for rapid onset of adverse effects and the need for multiple daily doses due to short tmax and t1/2. The newer MAOIs are a significant addition to therapy, as the rapid binding action of these medications increases their safety margin with regard to tyramine interactions. Further information in this area is required. In addition, moclobemide has pharmacokinetic features that are clinically beneficial (e.g. aging and renal dysfunction have little effect on the elimination of the drug), but also features that are not beneficial (e.g. nonlinear pharmacokinetics). Among the SSRIs, there are a range of t1/2 values for the parent drugs, from relatively short t1/2 values of less than 24 hours (paroxetine, fluvoxamine) to among the longest found (e.g. 2 days for fluoxetine). Only 2 of the agents (sertraline and citalopram) have linear pharmacokinetics, and 1 drug has nonlinear pharmacokinetics within the usual therapeutic range (fluvoxamine). Once a therapeutic blood concentration is established, linearity is helpful in avoiding the small dose changes and repeated rechecking of concentrations of medications that would be required for those agents with nonlinear pharmacokinetics. Sertraline stands out as having the best effects on behaviour among all antidepressants. However, fluoxetine and fluvoxamine are least likely to penetrate into breast milk. All 3 of the structurally unique newer antidepressants [amfebutamone (bupropion), viloxazine venlafaxine] have relatively short tmax values (1 to 2 hours), which may relate to the early onset of adverse effects. Amfebutamone has the benefits of linear pharmacokinetics with potential for defined therapeutic blood concentrations, lack of effect of liver enzymes on metabolism of the drug, and lack of significant effects of either aging or hepatic dysfunction on elimination of the drug. Thus, the antidepressants best suited for pharmacokinetic optimisation of ...

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Section: Imipraminementioning

confidence: 99%

Pharmacokinetic Optimisation of Therapy with Newer Antidepressants

Goodnick

1994

Clinical Pharmacokinetics

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“…These include individual variation in liver metabolism (Hammer & Sjoqvist, 1967;Alexanderson & Borga, 1973), plasma protein binding (Alexanderson & Borga, 1972;Glassman, Hurwic & Perel, 1973) and first pass metabolism (Gram & Christiansen, 1975). Most investigators, however, have assumed individual variation in gastrointestinal absorption to be unimportant (Haydu, Dhrymiotis & Quinn, 1962;Kragh-Ssrensen, Hansen & others, 1974). An opportunity to test the relative importance of individual variation in metabolism or absorption on tissue concentrations of imipramine (with its metabolites) was provided from data obtained in a study concerning the effects of tranquillizers on [l4C]imiprarnine pharmacokinetics (Beaubien, Mathieu & Coldwell, 1975).…”

Section: Health and Welfare Ottawa Ontario Canada Kia Ol2mentioning

confidence: 99%

Influence of stomach emptying rate on tissue radioactivity after [14C]imipramine in the rat

Beaubien¹,

Mathieu²

1976

Journal of Pharmacy and Pharmacology

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1derived from the BUT-viscosity curves for individual diminished in pathological states, may be expected to rabbits. It is apparent that none of the polymers offers reduce the concentration of exogenously applied polyoutstanding BUT at a viscosity acceptable for artificial mer solutions quite rapidly, and it is concluded that tears. The six commercial artificial tears tested gave materials capable of producing more stable artificial BUT values ranging from 64.5 s (s.e.m. 7.7) to 113.6 s pre-ocular films should be sought.(s.e. m. 18.4).June 18, 1975 Drainage and dilution by tear secretion, even when

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“…8 In at least one instance, the treatment of depressive reactions with imipramine, clinical results were inversely correlated with plasma levels of the drug. 3 It seems clear, therefore, that one cannot assume that blood levels reflect the degree of clinical action of all centrally acting drugs.…”

mentioning

confidence: 99%

Blood levels of pentobarbital sodium, meprobamate, and tybamate in relation to clinical effects

Hollister¹,

Clyde²

1968

Clin Pharma and Therapeutics

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Surprisingly few data are available for determining whether the serum concentration of a centrally acting drug is related to clinical activity. Although it is usually assumed that equilibration occurs between serum concentration of drugs and their concentration in the brain and cerebrospinal fluid, this assumption may not always he correct. Bromide intoxication is a case in which serum levels do not correlate well with clinical signs. Neither the level at which symptoms appear or disappear correlates well with absolute serum levels, l observations which have been substantiated by studies in animals.10 Serum levels of the phenothiazines are difficult to measure. When attempts have been made to measure serum levels of chlorpromazine, detectable levels are only tran-

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Plasma Imipramine Level in Syndromes of Depression

Cited by 25 publications

References 1 publication

Pharmacokinetic Optimisation of Therapy with Newer Antidepressants

Pharmacokinetic Optimisation of Therapy with Newer Antidepressants

Influence of stomach emptying rate on tissue radioactivity after [14C]imipramine in the rat

Blood levels of pentobarbital sodium, meprobamate, and tybamate in relation to clinical effects

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