Influence of hydration on ultrafilterable platinum kinetics and kidney function in patients treated with cis-diamminedichloroplatinum(II).
It has been reported that hypertonic saline provides protection against the renal toxicity of cisplatin (CDDP). We therefore evaluated its influence on the plasma and urinary pharmacokinetics of ultrafilterable platinum and kidney function as estimated by creatinine, inulin and PAH clearance. We undertook a randomized trial including two groups of ten patients receiving 100 mg/m2 CDDP in isotonic (group 1) or hypertonic saline (group 2) by a 20-min infusion. The hydration consisted of dextrose in group 1 and isotonic saline in group 2. Maximal concentration (Cmax), protein binding and cumulative urinary excretion were significantly higher in the dextrose group. Urinary flow decreased in this group but not in the other one. Inulin clearance was higher in the dextrose group than in the saline group and P-aminohippuric acid (PAH) clearance was not significantly different in these groups of patients. Hyponatremia was observed in the dextrose group. These results suggest that hypertonic saline infusion and saline hydration may enhance the diffusion of CDDP into tissues, lowering Cmax and renal excretion of platinum. The reduction of protein binding may indicate a diminution of aquation of CDDP in plasma. Our results suggest that the infusion of CDDP in hypertonic saline with salt hydration could exert a protective effect on the kidney. Moreover, there is a lessening of the risk of cellular hyperhydration. However, the better influence of dextrose hydration on glomerular filtration leads us to recommend a combination of the two methods of hydration for better tolerance and efficacy.
Dumas
M
M
Département de Pharmacologie Clinique, Hopital Général, Dijon, France.
de Gislain
C
C
d'Athis
P
P
Chadoint-Noudeau
V
V
Escousse
A
A
Guerrin
J
J
Autissier
N
N
D002712:Chlorides / Q000097:blood / Q000652:urine; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003404:Creatinine / Q000493:pharmacokinetics; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008657:Metabolic Clearance Rate; D010984:Platinum / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011897:Random Allocation; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage; D012964:Sodium / Q000097:blood / Q000652:urine; D014563:Urodynamics
D002712:Chlorides; D012462:Saline Solution, Hypertonic; D010984:Platinum; D007444:Inulin; D012964:Sodium; D003404:Creatinine; D005947:Glucose; D002945:Cisplatin