Continuous infusion of high-dose cisplatin in children: pharmacokinetics of free and total platinum.
A pharmacokinetic study was carried out in two infants and two (older) children with high-dose cisplatin (CP) (40 mg/m2/day) by 5-day continuous infusion. Following interruption of the infusion, the decrease in total plasma platinum was biphasic, with a terminal half-life of 155.5-418 h. During administration the urinary concentrations were between 7.66 and 15.2 mg/l. Thirty to thirty five per cent of the administered dose was eliminated within 48 h of discontinuing infusion. Free platinum (FP) levels declined in a biphasic manner, with a mean (+/- S.E.) elimination half-life of 81.25 (+/- 34.9) h. FP was still detectable in the plasma 10 days after the end of infusion with levels above 0.010 micrograms/ml. FP availability, measured as the area under the curves (AUC) of the FP concentration--up to 2 h after ending the infusion--were 768 (+/- 326) micrograms.min/ml. Inter- or intra-individual differences in AUC values were not observed.
Laboratoire Hospitalo-Universitaire de Pharmacocinétique, U278, Faculté de Pharmacie, Marseille, France.
M
M
Bues-Charbit
J C
JC
Gentet
J L
JL
Bernard
V
V
Breant
J P
JP
Cano
C
C
Raybaud
D002648:Child; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D007263:Infusions, Parenteral; D009447:Neuroblastoma / Q000378:metabolism*; D010984:Platinum / Q000097:blood* / Q000652:urine; D012208:Rhabdomyosarcoma / Q000378:metabolism*
D010984:Platinum; D002945:Cisplatin