Body Surface Area as a Determinant of Pharmacokinetics and Drug Dosing
Body surface area (BSA) was introduced intomedical oncology in order to derive a safestarting dose for phase I studies ofanticancer drugs from preclinical animaltoxicology data. It is not clear however,as to why dosing by BSA was extended to theroutine dosing of antineoplastic agents.Several formulas exist to estimate BSA, butthe formula derived by DuBois and DuBois isthe one used in adult medical oncology. This formula was derived based on data fromonly nine patients; subsequent attempts tovalidate the formula have found the DuBoisformula to either over or underestimate theactual determined BSA. While cardiacoutput does correlate with BSA, therelationship between BSA and otherphysiologic measures relevant for drugmetabolism and disposition, such as, renaland hepatic function, is weak ornonexistent. Further only epirubicin,etoposide, and carboplatin have beenstudied to determine if dosing by BSA wouldreduce interpatient variability, and noneof these drugs were found to havesignificant relationships between theirpharmacokinetics and BSA. Future clinicaltrials of new agents should not presumethat dosing based on BSA reducesinterpatient variability. Studies shouldexamine the role, if any, BSA has in dosingnew chemotherapeutic agents in initialphase I studies.
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