The pharmacokinetics of paroxetine in renal impairment

Doyle, Gerard; Laher, M; Kelly, John G.; Byrne, Maria; Clarkson, A. R.; Zussman, B. D.

doi:10.1111/j.1600-0447.1989.tb07181.x

Cited by 52 publications

(16 citation statements)

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“…However, the clearance of¯uvoxamine has not been assessed and 7 out of 25 patients discontinued prematurely due to gastrointestinal intolerance. For paroxetine, results of only a single oral 30 mg dose study have been reported showing a kinetic aberration in renal impairment aecting plasma levels of paroxetine and reducing the elimination t1 2 of the drug (Doyle et al, 1988). As high ®rst-pass metabolism of paroxetine renders usually less than 2 per cent of a given dose to be found in urine, these results could be interpreted as rather unexpected.…”

Section: Discussionmentioning

confidence: 91%

Mirtazapine oral single dose kinetics in patients with different degrees of renal failure

Bengtsson

Höglund

Timmer³

et al. 1998

Hum. Psychopharmacol. Clin. Exp.

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Section: Discussionmentioning

confidence: 91%

Mirtazapine oral single dose kinetics in patients with different degrees of renal failure

Bengtsson

Höglund

Timmer³

et al. 1998

Hum. Psychopharmacol. Clin. Exp.

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“…However, because the urinary route of excretion is more important with fluoxetine than sertraline (Benfield and Ward, 1986), the potential for renal impairment to adversely affect the pharmacokinetic profile of fluoxetine is higher compared with sertraline. Paroxetine, however, was shown to demonstrate increased (area under the concentration curve) AUC and Cmax with declining kidney function in a single-dose study (Doyle et al, 1989). Increases of 100-150% were seen in plasma levels with a glomerular filtration rate < 30 ml/min.…”

Section: Half-lifementioning

confidence: 94%

Selective serotonin reuptake inhibitors in affective disorders — I. Basic pharmacology

Goodnick¹,

1998

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The selective serotonin reuptake inhibitors (SSRIs), citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, are the result of rational research to find drugs that were as effective as the tricyclic antidepressants but with fewer safety and tolerability problems. The SSRIs selectively and powerfully inhibit serotonin reuptake and result in a potentiation of serotonergic neurotransmission. The property of potent serotonin reuptake appears to give a broad spectrum of therapeutic activity in depression, anxiety, obsessional and impulse control disorders. However, despite the sharing of the same principal mechanism of action, SSRIs are structurally diverse with clear variations in their pharmacodynamic and pharmacokinetic profiles. The potency for serotonin reuptake inhibition varies amongst this group, as does the selectivity for serotonin relative to noradrenaline and dopamine reuptake inhibition. The relative potency of sertraline for dopamine reuptake inhibition differentiates it pharmacologically from other SSRIs. Affinity for neuroreceptors, such as sigma1, muscarinic and 5-HT 2c , also differs widely. Furthermore, the inhibition of nitric oxide synthetase by paroxetine, and possibly other SSRIs, may have significant pharmacodynamic effects. Citalopram and fluoxetine are racemic mixtures of different chiral forms that possess varying pharmacokinetic and pharmacological profiles. Fluoxetine has a long acting and pharmacologically active metabolite. There are important clinical differences among the SSRIs in their pharmacokinetic characteristics. These include differences in their half-lives, linear versus non-linear pharmacokinetics, effect of age on their clearance and their potential to inhibit drug metabolising cytochrome P450 (CYP) isoenzymes. These pharmacological and pharmacokinetic differences underly the increasingly apparent important clinical differences amongst the SSRIs.

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“…However, when creatinine clearance reduces to less than 30 mllmin (1 .8 Llh), tmax increases slightly to 6.5 hours and tl/2 increases considerably to 29.7 hours. [ 171] In patients with hepatic dysfunction, available data indicate that there is a reduced tmax of 2.8 hours and a normal tl/ 2 of 18.9 hours.l I72 ] Alcoholic individuals have been found to have significantly more platelet-binding sites for paroxetine than controls' ! 173] Drug interactions are influenced by the significant effect of paroxetine on the CYP2D6 enzyme; its inhibition constant is 0.15, i.e.…”

Section: Paroxetinementioning

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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The pharmacokinetics of paroxetine in renal impairment

Cited by 52 publications

References 1 publication

Mirtazapine oral single dose kinetics in patients with different degrees of renal failure

Mirtazapine oral single dose kinetics in patients with different degrees of renal failure

Selective serotonin reuptake inhibitors in affective disorders — I. Basic pharmacology

Pharmacokinetic Optimisation of Therapy with Newer Antidepressants

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