Since the IC50 of uttroside B was 500 nM, the corresponding dose for animal studies was calculated as 10 mg/Kg using the formula, Dose in vivo = XY, where X = IC50 (in vitro) x molecular weight of the compound and Y = body weight x water content of the animal (0.6 for mice).
Fractional cholesterol absorption was calculated by the following formula: dose [C]:[H] − fecal [C]:[H]) / dose [C]:[H].
The total number of days delay per patient is shown in Figure 2, and the doses of capecitabine and gemcitabine delivered per cycle are shown in Figure 3. Using the formula: dose intensity = (cumulative dose received/duration of treatment)/ planned cumulative dose/planned duration of treatment), the achieved dose intensity for gemcitabine was 0.8, and for capecitabine was 0.76.
Nab-paclitaxel (100 mg/m) was given by i.v. drip infusion over a 30-min period in doses based on the body surface area (BSA) and calculated using the Mosteller formula; doses were given on days 1 and 8 for Levels 1 and 2b, and on days 1, 8, and 15 for Levels 2a and 3. 15 S-1 was given orally twice daily for 14 consecutive days, followed by a 7-day rest.
This dosing formula for conventional-dosed carboplatin has been approved by regulatory agencies, for example, FDA in 1997.
While dose model 1 estimates compressive forces by few simple formulas, dose model 2 uses comprehensive three-dimensional dynamic biomechanical simulations.
However, no data from an independent prospective study were available to validate our dosing formula.
Calvert et al (1989) presented a dosing formula to individualise the dose based on the patient's renal function, pretreatment with cytotoxic agents and chemotherapy protocol (monotherapy or combination therapy).
Although the Calvert dosing formula has been applied to high-dose treatment (Motzer et al, 2000), so far pharmacokinetic/pharmacodynamic analysis is rare (Huitema et al, 2002).
To estimate the predictive value of the dosing formula, we recalculated the daily phenprocoumon dose for each patient according to the regression equation (Fig. 3).
