Browsing by Subject "Voriconazole"

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  • Paajanen, Juuso; Halme, Maija; Palomäki, Maarit; Anttila, Veli-Jukka (2019)
    Scedosporium species are fungal opportunistic pathogens frequently seen in chronic lung diseases such as in cystic fibrosis (CF). They can cause a wide spectrum of diseases mainly in immunodeficient patients. Invasive, disseminated infections with poor prognosis have been described after lung transplantation. We present a CF-patient with disseminated Scedosporium apiospermum infection after lung transplantation. The patient had skin, surgical wound, spinal cord, and brain involvements. She recovered fully after prolonged course of voriconazole treatment.
  • Fihlman, Mari; Hemmilä, Tuija; Hagelberg, Nora M.; Backman, Janne T.; Laitila, Jouko; Laine, Kari; Neuvonen, Pertti J.; Olkkola, Klaus T.; Saari, Teijo I. (2018)
    PurposeBuprenorphine has low oral bioavailability. Regardless of sublingual administration, a notable part of buprenorphine is exposed to extensive first-pass metabolism by the cytochrome P450 (CYP) 3A4. As drug interaction studies with buprenorphine are limited, we wanted to investigate the effect of voriconazole, a strong CYP3A4 inhibitor, on the pharmacokinetics and pharmacodynamics of oral buprenorphine.MethodsTwelve healthy volunteers were given either placebo or voriconazole (orally, 400mg twice on day 1 and 200mg twice on days 2-5) for 5days in a randomized, cross-over study. On day 5, they ingested 0.2mg (3.6mg during placebo phase) oral buprenorphine. We measured plasma and urine concentrations of buprenorphine and norbuprenorphine and monitored their pharmacological effects. Pharmacokinetic parameters were normalized for a buprenorphine dose of 1.0mg.ResultsVoriconazole greatly increased the mean area under the plasma concentration-time curve (AUC(0-18)) of buprenorphine (4.3-fold, P
  • Fihlman, Mari; Hemmila, Tuija; Hagelberg, Nora M.; Kuusniemi, Kristiina; Backman, Janne T.; Laitila, Jouko; Laine, Kari; Neuvonen, Pertti J.; Olkkola, Klaus T.; Saari, Teijo I. (2016)
    This study aimed to determine possible effects of voriconazole and posaconazole on the pharmacokinetics and pharmacological effects of sublingual buprenorphine. We used a randomized, placebo-controlled crossover study design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6 mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily. Plasma and urine concentrations of buprenorphine and its primary active metabolite norbuprenorphine were monitored over 18 h and pharmacological effects were measured. Compared to placebo, voriconazole increased the mean area under the plasma concentration-time curve (AUC(0-a)) of buprenorphine 1.80-fold (90 % confidence interval 1.45-2.24; P <0.001), its peak concentration (C-max) 1.37-fold (P <0.013) and half-life (t (A1/2) ) 1.37-fold (P <0.001). Posaconazole increased the AUC0(0-a) of buprenorphine 1.25-fold (P <0.001). Most of the plasma norbuprenorphine concentrations were below the limit of quantification (0.05 ng/ml). Voriconazole, unlike posaconazole, increased the urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18-2.12; P <0.001) but there was no quantifiable parent buprenorphine in urine. Plasma buprenorphine concentrations correlated with the pharmacological effects, but the effects did not differ significantly between the phases. Voriconazole, and to a minor extent posaconazole, increase plasma exposure to sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P-glycoprotein. Care should be exercised in the combined use of buprenorphine with triazole antimycotics, particularly with voriconazole, because their interaction can be of clinical importance.