JAC Advance Access published online on March 24, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh175
© 2004 by The British Society for Antimicrobial Chemotherapy
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original article
1 The Paediatric and Adult
Cystic Fibrosis Units, St James’ and
Seacroft Hospitals, Leeds, UK
* Corresponding author. E-mail: steven.conway{at}leedsth.nhs.uk.
Received 18 September 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 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 ( 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
Pharmacokinetics and safety of itraconazole in
patients with cystic fibrosis
2 Department of Pharmacy, St James’ and
Seacroft Hospitals, Leeds, UK
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.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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|