TY - JOUR
T1 - Pharmacokinetics of cyclosporine as a function of energy-protein deficiency in children with chronic renal failure
AU - Lares-Asseff, Ismael
AU - Zaltzman, Samuel
AU - Pérez Guillé, María Gabriela
AU - Camacho, Guadalupe A.
AU - Murguía, Teresa
AU - López, María Del Carmen
AU - Toledo, Alejandra R.
AU - Zaltzman-Rudy, Amy B.
AU - Cravioto, Joaquín
PY - 1997/3
Y1 - 1997/3
N2 - The present study was conducted to determine whether malnutrition in patients with chronic renal failure requiring cyclosporine therapy for renal transplantation has some effect on the clinical pharmacokinetics of cyclosporine. Eleven pediatric patients were enrolled in this study before renal transplantation and divided into two groups (group I: six well- nourished patients with a deficit in weight/height ratio ≤ 7%; group II: five malnourished patients with a deficit in weight/height > 8%). The patients received a single oral dose of cyclosporine (3.0 mg/kg). Blood samples were collected for a 26-hour period, and serum concentrations of cyclosporine were measured using fluorescence-polarization immunoassay technology. The results suggest that, when malnutrition is present, the median C(max) of cyclosporine decreases by almost threefold (from 387.5 ng/mL in group 1 to 136.1 ng/mL in group II). An observed 52% reduction in AUC0- , (from 2,856.0 ng/mL/hr in group I to 1,481.4 ng/mL/hr in group II) was caused by the increased volume of distribution (from 4.6 L/kg in group I to 11.1 L/kg in group II). The elimination half-life (t( 1/4 )) was longer in group II compared with that of group I (12.4 hr for group II; range, 7.8-13.5 hr versus 8.9 hr for group I; range, 5.2-16.0 hr). Differences in t( 1/4 ) were not statistically significant at 5% confidence intervals. The effects of energy malnutrition on the pharmacokinetics of cyclosporine could explain in part some of the interindividual variability. This study provides pharmacokinetic guidelines for the use of cyclosporine.
AB - The present study was conducted to determine whether malnutrition in patients with chronic renal failure requiring cyclosporine therapy for renal transplantation has some effect on the clinical pharmacokinetics of cyclosporine. Eleven pediatric patients were enrolled in this study before renal transplantation and divided into two groups (group I: six well- nourished patients with a deficit in weight/height ratio ≤ 7%; group II: five malnourished patients with a deficit in weight/height > 8%). The patients received a single oral dose of cyclosporine (3.0 mg/kg). Blood samples were collected for a 26-hour period, and serum concentrations of cyclosporine were measured using fluorescence-polarization immunoassay technology. The results suggest that, when malnutrition is present, the median C(max) of cyclosporine decreases by almost threefold (from 387.5 ng/mL in group 1 to 136.1 ng/mL in group II). An observed 52% reduction in AUC0- , (from 2,856.0 ng/mL/hr in group I to 1,481.4 ng/mL/hr in group II) was caused by the increased volume of distribution (from 4.6 L/kg in group I to 11.1 L/kg in group II). The elimination half-life (t( 1/4 )) was longer in group II compared with that of group I (12.4 hr for group II; range, 7.8-13.5 hr versus 8.9 hr for group I; range, 5.2-16.0 hr). Differences in t( 1/4 ) were not statistically significant at 5% confidence intervals. The effects of energy malnutrition on the pharmacokinetics of cyclosporine could explain in part some of the interindividual variability. This study provides pharmacokinetic guidelines for the use of cyclosporine.
UR - http://www.scopus.com/inward/record.url?scp=0030939645&partnerID=8YFLogxK
U2 - 10.1002/j.1552-4604.1997.tb04779.x
DO - 10.1002/j.1552-4604.1997.tb04779.x
M3 - Artículo
C2 - 9089419
AN - SCOPUS:0030939645
SN - 0091-2700
VL - 37
SP - 179
EP - 185
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 3
ER -