Conversion and pharmacokinetic studies of a microemulsion formulation of cyclosporine in pediatric liver transplant patients.
A study of conversion from the standard cyclosporine treatment to a microemulsion formulation was performed in 29 stable pediatric liver transplant patients. The study was divided into conversion and in follow-up phases. While on therapy with the standard formulation at a mean daily dose+/-SD of 231+/-101.8 mg patients had a mean cyclosporine trough level of 188.7+/-51.4 ng/ml. Following a 1:1 conversion from the standard to the microemulsion formulation an increase in the cyclosporine trough level was observed in 75% of the patients. The mean cyclosporine trough level at this point was 221.5+/-69.7 ng/ml. On follow-up, the dose had to be reduced an average of 21.7% in 49% of the patients, whereas the rest remained stable. The incidence of adverse events was not significant and no differences were observed between the two formulations. The pharmacokinetic study of the microemulsion in 11 patients showed a monophasic curve, with an early absorption at 30 min and maximum concentration+/-SD of 880.8+/-72.8 ng/ml and time to maximum concentration of 1.5+/-0.12 hr. Basal time showed the least correlation with the area under the curve and T4 the most statistically significant. The microemulsion showed better bioavailability and pharmacokinetic characteristics than the standard formulation.
Department of Pediatrics, Hospital Italiano, Buenos Aires, Argentina.
D
D
D'Agostino
M
M
Gimenez
B
B
Yamaguchi
R
R
Glancszpigel
F
F
Vinuesa
M
M
Gamba
M
M
Ciardullo
E
E
de Santibaes
D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004361:Drug Tolerance; D004655:Emulsions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007223:Infant; D016031:Liver Transplantation / Q000276:immunology; D008297:Male; D008832:Microchemistry
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine