Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects

Saari, Teijo I.; Laine, Kari; Leino, Kari; Valtonen, Mika; Neuvonen, Pertti J.; Olkkola, Klaus T.

doi:10.1111/j.1365-2125.2006.02707.x

Cited by 20 publications

(10 citation statements)

References 20 publications

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“…It is plausible to assume that the observed pharmacokinetic changes are due to a marked decrease in the first-pass metabolism and plasma clearance of oxycodone because both the C max , AUC 0-∞ and t 1/2 of oxycodone were greatly increased by voriconazole, and these changes were accompanied by drastic changes in the metabolite-to-oxycodone ratios. Previous human studies have shown that voriconazole alters the pharmacokinetics of several drugs metabolized by CYP3A, including oral hypnotics [23][24][25] and opioids [26][27][28]. Voriconazole decreases the clearance of alfentanil by 83% [26] and that of fentanyl by 23% [27], and increases the AUC 0-24 of R-methadone by 47% [28].…”

Section: Discussionmentioning

confidence: 99%

Voriconazole drastically increases exposure to oral oxycodone

Hagelberg

Nieminen

Saari

et al. 2008

Eur J Clin Pharmacol

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Section: Discussionmentioning

confidence: 99%

Voriconazole drastically increases exposure to oral oxycodone

Hagelberg

Nieminen

Saari

et al. 2008

Eur J Clin Pharmacol

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“…Ci Phenytoin (CYP450 induction) 85,93 Significantly reduced increase voriconazole maintenance dose St. John's wort (CYP450 inducer) 103 Significantly reduced Ci Oral contraceptives containing ethinyl estradiol and norethindrone (CYP2C19 inhibition) 57 increased…”

Section: CImentioning

confidence: 99%

Pharmacotherapy of Invasive Fungal Infections with Voriconazole

Ghebremedhin

2011

Clinical Medicine Reviews in Therapeutics

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Voriconazole, a second-generation and broad-spectrum triazole derivative of fluconazole, inhibits the cytochrome P450 (CYP)-dependent enzyme 14-α-sterol demethylase, which is a pivotal step in cell membrane ergosterol synthesis in fungi. CYP2C19, CYP3A4, flavin-containing monooxygenase (FMO), and to a lesser extent CYP2C9 contribute to the oxidative metabolism of voriconazole by human liver microsomes. Clinical trials have demonstrated the safety and efficacy of voriconazole for prophylaxis and treatment in candidiasis, invasive aspergillosis, and in invasive fungal infections (IFIs) caused by a variety of non-Aspergillus molds, such as Fusarium or Scedosporium spp., and was generally well tolerated as primary therapy in adults and children. The availability of both parenteral and oral formulations and the nearly complete absorption (bioavailability of 96% for adults, ca. 40% in children) of the drug after oral administration provide for ease of use and potential cost savings, and ensure that the therapeutic plasma concentrations are maintained when switching from intravenous to oral regimes. It exhibits nonlinear pharmacokinetics in healthy controls and patients at high risk of IFIs, but considerable intra-and interpatient pharmacokinetic variability has raised the question of therapeutic drug monitoring. Most common adverse events are visual disturbances and elevated transaminase levels. The emergence of resistance towards voriconazole has been rarely reported.

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“…Clinically important drug interactions with zolpidem have been extensively reviewed. Drugs that inhibit or induce CYP isoenzymes may result in drug interactions with zolpidem (Swainston and Keatin 2005;Von Moltke et al 1999;Farkas et al 2009;Saari et al 2006;Cysneiros et al 2007;Villikka et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers

Vlase

Popa

Neag

et al. 2010

Eur J Drug Metab Pharmacokinet

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Our objective was to evaluate a possible pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers. The study consisted of two periods: Period 1 (reference), when each volunteer received a single dose of 5 mg zolpidem and Period 2 (test), when each volunteer received a single dose of 5 mg zolpidem and 500 mg ciprofloxacin. Between the two periods, the subjects were treated for 5 days with a single daily dose of 500 mg ciprofloxacin. Plasma concentrations of zolpidem were determined during a 12-hour period following drug administration. Pharmacokinetic parameters of zolpidem administered in each treatment period were calculated using non-compartmental analysis and the data from two periods were compared to determine statistically significant differences. In the two periods of treatments, the mean peak plasma concentrations (Cmax) were 75.73±28.34 ng/ml (zolpidem alone) and 80.58±22.40 ng/ml (zolpidem after pre-treatment with ciprofloxacin). The tmax, times taken to reach Cmax, were 0.91±0.42 and 1.44±0.61 h, respectively, and the total areas under the curve (AUC0-∞) were 300.2±115.5 and 438.1±142.6 ng h/ml, respectively. The half-life of zolpidem was 2.39±0.53 h when administered alone and 3.34±0.87 h after pre-treatment with ciprofloxacin. These differences were statistically significant for Cmax, tmax, AUC0-∞, half-life and mean residence time. Ciprofloxacin interacts with zolpidem in healthy volunteers, raising its bioavailability by about 46%. This magnitude of effect is likely to be clinically significant.

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Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects

Cited by 20 publications

References 20 publications

Voriconazole drastically increases exposure to oral oxycodone

Voriconazole drastically increases exposure to oral oxycodone

Pharmacotherapy of Invasive Fungal Infections with Voriconazole

Pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers

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