JAC Advance Access originally published online on March 24, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 841-847
© 2004 The British Society for Antimicrobial Chemotherapy
Pharmacokinetics and safety of itraconazole in patients with cystic fibrosis
1 The Paediatric and Adult Cystic Fibrosis Units and 2 Department of Pharmacy, St James’ and Seacroft Hospitals, Leeds, UK
Received 18 September 2003; returned 12 November 2003; revised 19 December 2003; accepted 10 February 2004
Objective: To assess the pharmacokinetics of itraconazole and hydroxy-itraconazole in patients with cystic fibrosis.
Methods: Patients were divided into those <16 and 
16 years of age. All received itraconazole oral solution 2.5 mg/kg twice daily for 14 days. Serial blood samples were taken for itraconazole and hydroxy-itraconazole plasma level measurements. Safety was assessed from biochemistry and haematology data and reported adverse events.
Results: Seventeen patients entered the study. Steady-state concentrations were achieved after maximally 8 days of dosing. On day 14 average peak plasma concentrations were 404 ± 268 ng/mL (<16 years, n = 5) and 779 ± 470 ng/mL (16 years, n = 11 excluding one patient concurrently receiving oral clarithromycin). A high inter-subject variability in itraconazole pharmacokinetics was seen. Intra-subject variability was low. All the younger patients and 50% of the older patients failed to achieve a plasma steady-state trough concentration of >250 ng/mL. Adverse events were reported by 53% of subjects. Most were mild or moderate in intensity and not considered related to treatment. One patient withdrew from the study because of two severe adverse events. Ten significant laboratory abnormalities were reported in seven of 16 patients with paired data. Six of these were clinically relevant.
Conclusion: 2.5 mg/kg itraconazole oral solution twice daily in patients with cystic fibrosis achieves steady-state concentrations in maximally 8 days. The pharmacokinetics showed marked inter-subject variability. Plasma concentrations of >250 ng/mL were not reached in the paediatric cohort or in 50% of the adult cohort. The dosage regimen was safe and well tolerated.
Keywords: allergic bronchopulmonary aspergillosis, antifungals, itraconazole
* Correspondence address. Seacroft Hospital, York Road, Leeds LS14 6UH, UK. Fax: +44-113-206-3738; E-mail: steven.conway{at}leedsth.nhs.uk
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  D. Shoseyov, K. G. Brownlee, S. P. Conway, and E. Kerem Aspergillus bronchitis in cystic fibrosis. Chest, July 1, 2006; 130(1): 222 - 226. [Abstract] [Full Text] [PDF]
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