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
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.