Differences in bioavailability between oral cyclosporine formulations in maintenance renal transplant patients

Citation
Jj. Curtis et al., Differences in bioavailability between oral cyclosporine formulations in maintenance renal transplant patients, AM J KIDNEY, 34(5), 1999, pp. 869-874
Citations number
12
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology
Journal title
AMERICAN JOURNAL OF KIDNEY DISEASES
ISSN journal
0272-6386 → ACNP
Volume
34
Issue
5
Year of publication
1999
Pages
869 - 874
Database
ISI
SICI code
0272-6386(199911)34:5<869:DIBBOC>2.0.ZU;2-#
Abstract
Previous studies of healthy volunteers and small numbers of transplant reci pients have suggested that the oral solution formulation of Sandimmune (cyc losporine [CsA]; Sandoz Pharmaceuticals, East Hanover, NJ) is bioequivalent to the soft gelatin capsule (SGC) formulation, However, there is conflicti ng evidence as to whether the two formulations are bioequivalent in all pat ients; to date, there are no published studies that explicitly address thei r bioequivalence in patients. We conducted a randomized, open-label, two-se quence, two-period, crossover study. Of 20 maintenance renal transplant rec ipients shown by a screening pharmacokinetic (PK) profile to be poor absorb ers of CsA, half were randomized to receive first the SGC formulation and h alf the oral solution formulation for a period of 7 days, Each patient then underwent a la-hour PK profile on the last day of the assigned formulation before a crossover to receive the other formulation and repeat the 7-day t reatment and PK profile cycle. The results showed that peak and total expos ure to CsA was greater with the SGC formulation, The SGC-oral solution rati os indicated an average 38% greater peak and 11% greater total exposure for the SGC formulation (P < 0.01 and P = 0.09, respectively). Trough levels w ere more similar between formulations, with SGC showing an average of 5% gr eater troughs (P > 0.10). In our selected population of malabsorbers, the S GC formulation made a difference in drug exposure. (C) 1999 by the National Kidney Foundation, Inc.