Relative bioavailability of deferasirox tablets administered without dispersion and dispersed in various drinks.
Deferasirox (ExjadeA, ICL670) is a new, once-daily oral iron chelator, recently approved as first-line therapy in the treatment of iron overload resulting from blood transfusions. In registration studies, deferasirox tablets were dispersed in non-carbonated water prior to administration. In routine clinical practice, however, patients may prefer to take the tablet dispersed in a flavored drink rather than with water.


OBJECTIVE
Stability and compatibility tests were performed to identify beverages suitable for the dispersion of tablets for further testing in man. This was followed by a pharmacokinetic study to assess the relative bioavailability of deferasirox tablets dispersed in two types of soft drinks, dispersed in water, and without dispersion.


METHODS
An open-label, randomized, 4-period, crossover study was carried out with 28 healthy volunteers who received single 20 mg/kg oral doses of deferasirox without dispersion, dispersed in orange juice, dispersed in apple juice and dispersed in non-carbonated water (reference). Deferasirox and Fe-[deferasirox]2 were measured in plasma using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were compared using standard bioequivalence tests.


RESULTS
Mean deferasirox AUC0-t were 1,040 A+/- 530, 1,010 A+/- 278, 882 A+/- 252 and 996 A+/- 352 h x micromol/l when deferasirox tablets were administered without dispersion, dispersed in orange juice, dispersed in apple juice and dispersed in water, respectively, indicating that these forms of deferasirox administrations met bioequivalence criteria. Therefore, the oral bioavailability of deferasirox tablets was not affected neither by the degree of dispersion nor by the type of drink (orange or apple juice versus water) used for dispersion.


CONCLUSIONS
This study shows that deferasirox bioavailability is unaltered when dispersed with orange or apple juice compared with dispersion in water. Thus, in addition to water, patients have the option of taking deferasirox tablets in orange or apple juice. The degree of dispersion did not affect deferasirox bioavailability. Therefore, deferasirox therapy will not be compromised if dispersion of the tablet is not fully complete; although the latter should be avoided.
Séchaud
R
R
Novartis Pharma AG, Basel, Switzerland. romain.sechaud@novartis.com
Dutreix
C
C
Balez
S
S
Pommier
F
F
Dumortier
T
T
Morisson
S
S
Brun
E
E
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001565:Benzoates / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001628:Beverages; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D032084:Citrus sinensis; D018592:Cross-Over Studies; D000077588:Deferasirox; D003967:Diarrhea / Q000139:chemically induced; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D027845:Malus; D013607:Tablets; D053719:Tandem Mass Spectrometry; D014230:Triazoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D014867:Water / Q000008:administration & dosage / Q000737:chemistry*
D001565:Benzoates; D007502:Iron Chelating Agents; D013607:Tablets; D014230:Triazoles; D014867:Water; D000077588:Deferasirox