Calvert Formula

Pharmacokinetic-pharmacodynamic correlations between AUC, response rates, and the extent of myelosuppression have been examined retrospectively in patients with advanced ovarian carcinoma (21,24). AUC values below 4 minutes/mg/ml and exceeding 7 minutes/mg/ml cannot be recommended the former is associated with low response rates and the latter is associated with more pronounced neutropenia and thrombocytopenia without higher response rates. Doses of carboplatin are generally calculated by the Calvert formula (26) ... 

Calvert formula for dose modifications Dose (mg) = target AUC x (CLcr -E 25) CIcr calculated using Cockcroft-Gault equation note that the calculated dose is total dose, not dose per m body surface area Bone marrow recovery may require 6-8 weeks postadministration not a vesicant vein irritation and facial flushing may be related to alcohol vehicle... 

Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage Prospective evaluation of a simple formula based on renal function. J Clin Oncol 1989 7( 11) 1748-1756. 

A concern with AUC-targeting based on renal function surrounds the measurement of creatinine clearance. The formulas of Calvert et al. were developed using EDTA clearance, measurement of which is not widely available. They have shown that neither standard measured creatinine clearance, nor the calculation of this index are as accurate or as reproducible. To circumvent this difficulty an alternative dosing strategy has been developed by Chatelut, Canal and co-workers [226], This dosing approach is being tested in clinical trials. 

The dose administered should be adjusted in proportion to the reduction of creatinine clearance for patients with renal impairment since they require lower doses to achieve AUCs comparable with those seen with patients with normal renal function. Calvert et al. [64] have proposed the following formula for calculation of dose ... 

The philosophy of Wyllie s time-average formula (see Section 6.6.2) leads to the CRIM or Complex Refractive Index Method formula (Calvert et al., 1977). The time-average equation is explained as a summation of the travel time of the signal passing the solid matrix and the pore fluid both rock components are condensed as a layer. 

---