Effect of Carbamazepine on the Single Oral Dose Pharmacokinetics of Alprazolam

Furukori, Hanako; Otani, Koichi; Yasui, Norio; Kondo, Tsuyoshi; Kaneko, Sunao; Shimoyama, Ritsuko; Ohkubo, Tadashi; Nagasaki, T.; Sugawara, Kazunobu

doi:10.1016/s0893-133x(97)00166-8

Cited by 46 publications

(16 citation statements)

References 27 publications

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“…In the present two studies, however, the pharmacokinetics of alprazolam in all subjects were unchanged even after repeated ingestion of grapefruit juice, although CYP3A4 is involved to a major extent in the metabolism of alprazolam (von Moltke et al 1994;Yasui et al 1996;Furukori et al 1998). Grapefruit juice might not increase the bioavailability of alprazolam due to its high bioavailability (92%; Greenblatt and Wright 1993).…”

Section: Discussioncontrasting

confidence: 55%

Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam

et al. 2000

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The effects of repeated ingestion of grapefruit juice, an inhibitor of cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of both single and multiple oral doses of alprazolam, a substrate of CYP3A4, were examined. In study 1, eight healthy volunteers ingesting 600 ml/day water or grapefruit juice for 10 days took a single oral 0.8-mg dose of alprazolam on the eighth day. Plasma drug concentrations were monitored up to 48 h after alprazolam dosing together with evaluation of psychomotor function. Grapefruit juice altered neither the plasma concentrations of alprazolam at any time points, any pharmacokinetic parameters, nor the majority of psychomotor function parameters in subjects. In study 2, 11 patients with anxiety disorders receiving alprazolam (0.8-2.4 mg/day) ingested grapefruit juice (600 ml/day) for 7 days. Blood samples were collected before and during grapefruit juice ingestion and 1 week after its discontinuation together with an assessment of clinical status. Grapefruit juice altered neither the steady-state plasma concentration of alprazolam nor the clinical status in patients. The present study shows that grapefruit juice is unlikely to affect pharmacokinetics or pharmacodynamics of alprazolam due to its high bioavailability.

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Section: Discussioncontrasting

confidence: 55%

Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam

et al. 2000

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“…The AUCs were decreased by 17%, an amount that could be clinically significant for drugs with narrow therapeutic indices. However, when the effects of GB are compared with synthetic medications known to induce ALPZ metabolism such as carbamazepine 14 and rifampin, 12 the magnitude of GB effects were quite small and not likely to be clinically significant for most widely used drugs.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] It is characterized by a low hepatic extraction ratio and high bioavailability 13 and has been used by our group and others to clinically assess both CYP3A4 inhibition and induction. 12,14 MATERIALS AND METHODS…”

mentioning

confidence: 99%

Multiple-Dose Administration of Ginkgo biloba Did Not Affect Cytochrome P-450 2D6 or 3A4 Activity in Normal Volunteers

Markowitz¹,

Donovan²,

DeVane³

et al. 2003

Journal of Clinical Psychopharmacology

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Standardized extracts from the Ginkgo biloba tree are purported to exert positive neurocognitive effects and may also be useful in the treatment of a variety of vascular and other disorders. This dietary supplement is among the most commonly used herbal preparations in the world. The objective of this study was to assess in normal volunteers (n = 12) the influence of standardized Ginkgo biloba (GB) on the activity of cytochrome P-450 (CYP) 2D6 and 3A4 normal volunteers phenotyped as CYP2D6 extensive metabolizers. Probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP 3A4 activity) were co-administered orally at baseline, and following treatment with GB (120 mg twice daily) for 14 days. Urinary concentrations of dextromethorphan and dextrorphan were quantified and dextromethorphan metabolic ratios (DMRs) were determined at baseline and after GB treatment. Likewise, plasma samples were collected (0-60 hrs) for alprazolam pharmacokinetics at baseline and after GB treatment to assess effects on CYP 3A4 activity. Validated HPLC methods were used to quantify all compounds and relevant metabolites. No statistically significant differences were found between baseline and post-GB treatment DMRs indicating a lack of effect on CYP2D6. For alprazolam there was a 17% decrease in the area under the plasma concentration versus time curve (AUC); (P<0.05). However, the half-life of elimination was not significantly different after GB administration indicating a lack of hepatic CYP3A4 induction. We conclude that standardized extracts of GB at recommended doses are unlikely to significantly alter the disposition of co-administered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination.

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“…DSST and symbol copying were not affected by alprazolam and venlafaxine combined (3). Test performance (DSST and RT tasks) after alprazolam are worsened by drugs that alter CYP3A4 metabolism, including nefazodone (112,154), fluoxetine (107,160), fluvoxamine (91), carbamazepine (97), cimetidine (1,207), and propoxyphene (2).…”

Section: Interactions With Cyp3a4 Inhibitorsmentioning

confidence: 99%

Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature

2004

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Alprazolam is a benzodiazepine derivative that is currently used in the treatment of generalized anxiety, panic attacks with or without agoraphobia, and depression. Alprazolam has a fast onset of symptom relief (within the first week); it is unlikely to produce dependency or abuse. No tolerance to its therapeutic effect has been reported. At discontinuation of alprazolam treatment, withdrawal and rebound symptoms are common. Hence, alprazolam discontinuation must be tapered. An exhaustive review of the literature showed that alprazolam is significantly superior to placebo, and is at least equally effective in the relief of symptoms as tricyclic antidepressants (TCAs), such as imipramine. However, although alprazolam and imipramine are significantly more effective than placebo in the treatment of panic attacks, Selective Serotonin Reuptake Inhibitors (SSRIs) appear to be superior to either of the two drugs. Therefore, alprazolam is recommended as a second line treatment option, when SSRIs are not effective or well tolerated. In addition to its therapeutic effects, alprazolam produces adverse effects, such as drowsiness and sedation. Since alprazolam is widely used, many clinical studies investigated its cognitive and psychomotor effects. It is evident from these studies that alprazolam may impair performance in a variety of skills in healthy volunteers as well as in patients. Since the majority of alprazolam users are outpatients, this behavioral impairment limits the safe use of alprazolam in patients routinely engaged in potentially dangerous daily activities, such as driving a car.

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Effect of Carbamazepine on the Single Oral Dose Pharmacokinetics of Alprazolam

Cited by 46 publications

References 27 publications

Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam

Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam

Multiple-Dose Administration of Ginkgo biloba Did Not Affect Cytochrome P-450 2D6 or 3A4 Activity in Normal Volunteers

Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature

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