Carboplatin clearance

Benezet, S., Guimbaud, R., Catelut, E., Chevreau, C., Bugat, R., and Canal, P. How to predict carboplatin clearance from standard morphological and biological characteristics in obese patients. Annals of Oncology 1997 6 607-609. 

Chatelut, E., Canal, R, Brunner, V., Chevreau, C., Pujol, A., Boneu, A., Roche, H., Houin, G. and Bugat, R., Prediction of carboplatin clearance from standard morpho-logical and biological patient characteristics, /. Natl. Cancer Inst., 87(8), 573, 1995. 

Chatelut E et al. Prediction of carboplatin clearance from standard morphological and biological patient characteristics. J Natl Cancer Inst 1995 87 573-580. 

Carboplatin displays less nephro-, oto- and neurotoxicity. However, myelosuppression is more frequent, and as the drug is exclusively cleared through the kidney, adjustment of dose for creatinine clearance must be accomplished. 

Table 5 Hydroylsis and plasma clearance half-lives for cisplatin and carboplatin ...

MUd to moderate reduction in creatinine clearance with rises in serum urea and creatinine were reported in 14% of patients receiving carboplatin in a dose of 400 mg/m for gynecological malignancies. Of the patients who received carboplatin 400 mg/m with vincristine but without hydration for lung cancer, 19% developed renal changes. 

Tissue distribution is similar to that seen with cisplatin with the highest concentrations of platinium in the kidney, liver, skin and tumors [53]. Tissue platinium concentrations were generally 0.5 to 3 fold greater than those observed after cisplatin. It has been demonstrated that platin which is bound to plasma protein looses most of its cytotoxicity [54]. In contrast to cisplatin, which is extensively protein bound, carboplatin appears to be less extensively bound [15 to 25%] at least in the initial hours following administration. Renal clearance appears to be the main route of excretion, and urinary excretion of carboplatin is more rapid than that of cisplatin in animals [55] and cancer patients [56]. 50 to 80% of the dose administered is excreted in the urine over the first 24 hours [57,58,59]. It has been postulated that repeated administration of cisplatin may cause decreased carboplatin renal clearance and enhanced toxicity [60]. Renal clearance and total body clearances are reduced in patients with reduced renal function [61, 62, 63]. 

Plasma clearance of carboplatin is biphasic. with up to hS% excreted in the urine. There is little bound to plasma ] fitDleins and no true metabolism. 

Tissue distribution is similar to that seen with cisplatin with the highest concentrations of platinum in the kidney, liver, skin and tumors [53]. Tissue platinum concentrations were generally 0.5 to 3 fold greater than those observed after cisplatin. However, once platinum is bound to plasma protein its cytotoxicity is substantially reduced [54]. In contrast to the extensively protein binding of cisplatin, carboplatin is only 15 to 25% bound during the initial hours following administration. Renal clearance appears to be the main route... 

The dose of carboplatin should be adjusted in proportion to the reduction in creatinine clearance for patients with a creatinine clearance <60 mUmin. 

The formation clearance of thiotepa was 33% lower and exposure to the active metabolite TEPA (triethylenephosphamide) was 20% lower in 6 patients receiving aprepitant with a 4-day course of high-dose CTC (cyclophosphamide, thiotepa, carboplatin) when compared with 49 patients receiving high-dose CTC without aprepitant. ... 

The clearance of etoposide may be modestly reduced by carboplatin and cispiatin, but this is probably unlikely to be clinically relevant. 

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