Lack of Effect of Sertraline on the Pharmacokinetics of Alprazolam

Preskorn, Sheldon; Greenblatt, David J.; Harvey, Anne T.

doi:10.1097/00004714-200010000-00020

Cited by 10 publications

(4 citation statements)

References 5 publications

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“…In the broad sense, there is evidence suggesting that nefazodone, 25 fluoxetine, 26,27 and fluvoxamine 28 are significant in vivo inhibitors of alprazolam metabolism, thus potentially increasing the risk of inducing alprazolam central nervous system side effects. Conversely, venlafaxine, 29 sertraline, [30][31][32] and, according to the present study, paroxetine have demonstrated no in vivo inhibition of CYP3A4-mediated alprazolam metabolism.…”

Section: Discussionsupporting

confidence: 40%

Lack of Pharmacologic Interaction Between Paroxetine and Alprazolam at Steady State in Healthy Volunteers

Calvo¹,

García-Gea²,

Luque³

et al. 2004

Journal of Clinical Psychopharmacology

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This investigation aimed to provide evidence on the lack of pharmacokinetic interaction of paroxetine (20 mg/d) and alprazolam (1 mg/d) in combined therapy. In addition, the central effects of both drugs when administered alone and in combination were assessed to rule out any relevant synergistic depressant central effect. Twenty-five healthy young adult volunteers participated in a double-blind, double-dummy, placebo-controlled, repeated dose (15 days), 4-period crossover study. Each subject received each of 4 treatment sequences (ie, paroxetine-alprazolam placebo, alprazolam-paroxetine placebo, paroxetine-alprazolam, and paroxetine placebo-alprazolam placebo) in randomized order. The ratios for area under the curve within a dosing interval and maximum plasma concentration of the paroxetine plus alprazolam sequence to single agent paroxetine were 1.07 (90% confidence interval = 0.99 to 1.16) and 1.05 (90% confidence interval = 0.97 to 1.13), respectively, with no statistically significant differences between the 2 treatments. Similarly, for alprazolam, ratios for the combined to the single treatment sequence were 0.99 (90% confidence interval = 0.93 to 1.05) and 1.00 (90% confidence interval = 0.94 to 1.07) for area under the curve within a dosing interval and maximum plasma concentration, respectively, showing no evidence for interaction. Comparative pharmacodynamics on the combination was assessed using 6 Psychomotor Performance Tests and 5 Visual Analogue Scales focused on mood variables. Alprazolam and paroxetine plus alprazolam induced similar and significant performance impairment and sedation after both single and repeated dose administration, being less evident on day 15. After dosing, paroxetine plus alprazolam showed a lower recovery pattern than alprazolam alone, especially on day 15. No treatment sequence showed cumulative effects after repeated dose administration. Psychomotor Performance Tests and Visual Analogue Scales data suggested lack of pharmacodynamic interactions. Accordingly, study results showed no evidence for pharmacologic interactions between paroxetine and alprazolam at steady state. The most commonly reported adverse event was drowsiness, with a higher incidence under both single and combined alprazolam treatments.

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Section: Discussionsupporting

confidence: 40%

Lack of Pharmacologic Interaction Between Paroxetine and Alprazolam at Steady State in Healthy Volunteers

Calvo¹,

García-Gea²,

Luque³

et al. 2004

Journal of Clinical Psychopharmacology

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“…Interactions between alprazolam and antidepressants have been particularly studied, due to the high frequency of co-administration, and most secondgeneration antidepressants, such as SSRIs (selective serotonin reuptake inhibitors), have been tested for this purpose. No interaction has been found between alprazolam and the SSRIs paroxetine [23] and sertraline [24] in healthy volunteers. Fluoxetine, an SSRI antidepressant and an inhibitor of CYP3A4, prolongs by 16% the half-life and increases by 32% the AUC of alprazolam [23].…”

Section: -Metabolism and Pharmacokineticsmentioning

confidence: 86%

Benzodiazepine Metabolism: An Analytical Perspective

Mandrioli¹,

Mercolini²,

Raggi

2008

CDM

139

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Benzodiazepines are currently among the most frequently prescribed drugs all over the world. They act as anxiolytics, sedatives, hypnotics, amnesics, antiepileptics and muscle relaxants. Despite their common chemical scaffold, these drugs differ in their pharmacokinetic and metabolic properties. In particular, they are biotransformed by different cytochrome P450 isoforms and also by different UDP-glucuronosyltransferase subtypes. The most important studies on the metabolic characteristics of several 1,4-benzodiazepines, carried out from 1998 onwards, are reported and briefly discussed in this review. Moreover, the analytical methods related to these studies are also described and commented upon and their most important characteristics are highlighted. Most methods are based on liquid chromatography, which provides wide applicability and good analytical performance granting high precision, accuracy and feasibility. Mass spectrometry is gaining widespread acceptance, particularly if the matrix is very complex and variable, such as human or animal blood. However, spectrophotometric detection is still used for this purpose and can grant sufficient selectivity and sensitivity when coupled to suitable sample pre-treatment procedures. A monograph is included for each of the following benzodiazepines: alprazolam, bromazepam, brotizolam, clotiazepam, diazepam, etizolam, flunitrazepam, lorazepam, midazolam, oxazepam and triazolam.

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“…19 Two studies later showed that sertraline does not inhibit metabolism of ALPZ in humans. 20,21 Finally, nefazodone 22 is a substantial inhibitor of CYP3A4 substrate metabolism in vivo and increased the single-dose and multiple-dose AUC of ALPZ in healthy volunteers. The inhibitory effect of nefazodone is partly due to metabolites.…”

mentioning

confidence: 99%

Comparative CYP3A4 Inhibitory Effects of Venlafaxine, Fluoxetine, Sertraline, and Nefazodone in Healthy Volunteers

DeVane

Donovan²,

Liston³

et al. 2004

Journal of Clinical Psychopharmacology

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An antidepressant for use in the patient receiving concomitant drug treatment, over-the-counter medications, or herbal products should lack cytochrome P-450 (CYP) 3A4 inductive or inhibitory activity to provide the least likelihood of a drug-drug interaction. This study addresses the potential of 4 diverse antidepressants (venlafaxine, nefazodone, sertraline, and fluoxetine) to inhibit or induce CYP3A4. In a 4-way crossover design, 16 subjects received clinically relevant doses of venlafaxine, nefazodone, or sertraline for 8 days or fluoxetine for 11 days. Treatments were separated by a 7- to 14-day washout period and fluoxetine was always the last antidepressant taken. CYP3A4 activity was evaluated for each subject at baseline and following each antidepressant using the erythromycin breath test (EBT) and by the pharmacokinetics of alprazolam (ALPZ) after 2-mg dose of oral ALPZ. Compared to baseline, venlafaxine, sertraline, and fluoxetine caused no apparent inhibition or induction of erythromycin metabolism (P > 0.05). For nefazodone, a statistically significant inhibition was observed (P < 0.0005). Nefazodone was also the only antidepressant that caused a significant change in ALPZ disposition, decreasing its area under the concentration-versus-time curve (AUC; P < 0.01), and increasing its elimination half-life (16.4 vs. 12.3 hours; P < 0.05) compared with values at baseline. No significant differences were found in the pharmacokinetics of ALPZ with any of the other antidepressants tested. These results demonstrate in vivo that, unlike nefazodone, venlafaxine, sertraline, and fluoxetine do not possess significant metabolic inductive or inhibitory effects on CYP3A4.

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Lack of Effect of Sertraline on the Pharmacokinetics of Alprazolam

Cited by 10 publications

References 5 publications

Lack of Pharmacologic Interaction Between Paroxetine and Alprazolam at Steady State in Healthy Volunteers

Lack of Pharmacologic Interaction Between Paroxetine and Alprazolam at Steady State in Healthy Volunteers

Benzodiazepine Metabolism: An Analytical Perspective

Comparative CYP3A4 Inhibitory Effects of Venlafaxine, Fluoxetine, Sertraline, and Nefazodone in Healthy Volunteers

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