Pharmacokinetics of an oral solution of the microemulsion formulation of cyclosporine in maintenance pediatric liver transplant recipients.
BACKGROUND
A comparison of the oral bioavailability of cyclosporine from the original formulation (CsA) and from the new formulation, cyclosporine for microemulsion (CsA-ME), was made in pediatric maintenance liver transplant patients within two age groups (group 1, ages 1-5 years; group 2, ages 6-17 years) in an open-label, multicenter, randomized crossover trial. All patients were at least 6 months past transplantation and were receiving CsA maintenance therapy.


METHODS
In study period 1 (days 1 through 14), patients were administered either CsA or CsA-ME at the same b.i.d. dosage as their maintenance therapy. Upon entry into period 2 (days 15 through 28), patients were converted to the alternate formulation at a 1:1 mg dose ratio. On day 29, all patients returned to the CsA treatment administered at study entry, with follow-up on day 35. Dosage adjustments were not allowed with either CsA or CsA-ME. Twelve-hour pharmacokinetic profiling was performed at the end of periods 1 and 2.


RESULTS
Both the mean area under the concentration-versus-time curve and the mean maximum blood concentration of cyclosporine-both normalized for dose-were significantly increased: by 66% and 109%, respectively, in patients receiving CsA-ME compared with those receiving CsA in group 1 and by 39% and 75%, respectively, in group 2. During this study, liver function remained stable, and serum creatinine and blood pressure did not differ significantly between treatment groups.


CONCLUSIONS
This study shows increased bioavailability in all patients converted to CsA-ME, with the greatest increase seen in patients with the lowest initial cyclosporine bioavailability. The tolerability was similar between the two formulations during this study.
Dunn
S
S
Department of Surgery, St. Christopher's Hospital for Children, Temple University School of Medicine, Philadelphia, Pennsylvania 19134, USA.
Cooney
G
G
Sommerauer
J
J
Lindsay
C
C
McDiarmid
S
S
Wong
R L
RL
Chang
C T
CT
Smith
H T
HT
Choc
M G
MG
D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004655:Emulsions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007223:Infant; D016031:Liver Transplantation; D008297:Male
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine