Pharmacokinetics and dose adjustment of carboplatin

Carboplatin differs from cisplatin by its pharmacokinetics and toxicity pro file. Carboplatin is mainly eliminated by the kidneys and its dose-limiting toxicity is the bone marrow suppression. Myelosuppression of carboplatin i s more closely correlated with the area under the curve (AUC) of ultrafiltr able plasma concentration versus time to which a patient is exposed, than i t is with the administered dose. Similar relationships have been shown betw een A UC and antitumour effect, although they are in a smaller number and l ess close. Several method of dosage individualisation a priori (before carb oplatin administration) have been proposed. Since carboplatin is often pres cribed to patients with altered renal functions, this dose optimisation is particularly justified. Dose individualisation is based on both equations a llowing to predict the patient carboplatin clearance and the choice of targ et A UC. The different equations proposed are bared on direct measurement o f the renal filtration glomerular rate or an patient demographic and biolog ical characteristics such as weight and serum creatinine. The respective ad vantages and limits of these equations are now well known. However, the val ues of optimal AUC that depend on cytotoxic drugs combined to carboplatin a nd the patient hematopoietic status, are not precisely determined for each protocol of chemotherapy. When carboplatin is given by reiterated administr ations within each course, it is possible to adjust the last doses accordin g to a limited number of blood samples following the first infusion and a B ayesian analysis of the observed plasma concentrations. These methodologies are more complex, but they may be useful for the intensification protocols Carboplatin is still the only cytotoxic drug for which dose is individuali sed not according to the body surface area but according to pharmacokinetic parameters.