Evista Clinical Pharmacology

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Evista - Clinical Pharmacology [Raloxifene]

Unconjugated raloxifene comprises less than 1% of the total radiolabeled material in plasma. The terminal log-linear portions of the plasma concentration curves for raloxifene and the glucuronides are generally parallel. This is consistent with interconversion of raloxifene and the glucuronide metabolites.

Following intravenous administration, raloxifene is cleared at a rate approximating hepatic blood flow. Apparent oral clearance is 44.1 L/ kg° hr. Raloxifene and its glucuronide conjugates are interconverted by reversible systemic metabolism and enterohepatic cycling, thereby prolonging its plasma elimination halflife to 27.7 hours after oral dosing.

Results from single oral doses of raloxifene predict multiple-dose pharmacokinetics. Following chronic dosing, clearance ranges from 40 to 60 L/ kg° hr. Increasing doses of raloxifene HCl (ranging from 30 to 150 mg) result in slightly less than a proportional increase in the area under the plasma time concentration curve (AUC).

Excretion Raloxifene is primarily excreted in feces, and less than 0.2% is excreted unchanged in urine. Less than 6% of the raloxifene dose is eliminated in urine as glucuronide conjugates.

Table 1. Summary of Raloxifene Pharmacokinetic Parameters in the Healthy Postmenopausal Woman Cmax a (ng/ mL)/ (mg/ kg) t1/ 2 (hr) AUC0
a (ng?hr/ mL)/ (mg/ kg) CL/ F (L/ kg?hr) V/ F (L/ kg)

Single Dose Mean 0.50 27.7 27.2 44.1 2348
CV (%) 52 10.7 to 273 b 44 46 52 Multiple Dose
Mean 1.36 32.5 24.2 47.4 2583 CV (%) 37 15.8 to 86.6 b 36 41 56
Abbreviations: Cmax = maximum plasma concentration, t1/ 2 = half-life, AUC = area under the curve, CL = clearance, V = volume of distribution, F = bioavailability, CV = coefficient of variation.
a Data normalized for dose in mg and body weight in kg.
b Range of observed half-life.

Special Populations Geriatric ?

No differences in raloxifene pharmacokinetics were detected with regard to age (range 42 to 84 years).