Pharmacokinetics of oral cyclosporin A in diabetic children and adolescents.
Cyclosporin A (CsA) pharmacokinetics was studied in 19 diabetic children (mean age: 10.6 y). They were divided into prepubertal (I) and pubertal (II) groups according to plasma oestradiol or testosterone concentrations. The kinetic study was performed after a 72 h wash out period and a single oral dose of 7.5 mg/kg CsA. CsA in blood was measured by HPLC. The kinetic parameters: Cmax, tmax, t 1/2, AUC, CL/f, Vz/f and tss were calculated. No significant difference was found between the two groups. A significant negative correlation was found between Vz and both total cholesterol (r = -0.46), VLDL + LDL - cholesterol (r = -0.49) and VLDL + LDL - phospholipids (r = -0.58). CsA kinetics at steady-state were simulated by superimposition of single dose kinetics derived from each single dose. Measured steady-state blood concentrations were correlated (r = 0.80) with the values predicted by the simulation. The results suggest that CsA adjustment dosage of the CsA may be performed after a single oral dose using blood levels measured by HPLC. This procedure requires validation in further studies.
Misteli
C
C
Département de Pharmacologie Périnatale et Pédiatrique, Hôpital Saint-Vincent de Paul, Paris, France.
Rey
E
E
Pons
G
G
Richard
M O
MO
d'Athis
P
P
Legrand
A
A
Bougneres
P
P
Olive
G
G
D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003920:Diabetes Mellitus / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D006801:Humans; D010743:Phospholipids / Q000097:blood; D013739:Testosterone / Q000097:blood
D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D003524:Cyclosporins; D010743:Phospholipids; D013739:Testosterone; D004958:Estradiol