OBJECTIVE: To determine the effect of sunitinib (Sutent; SU11248; Pfizer), a US Food and Drug Administration-approved receptor tyrosine kinase inhibitor previously shown to reduce de novo pelvic adhesion formation, on reproductive function after surgical uterine abrasion in a rabbit model. DESIGN: Randomized placebo-controlled study. SETTING: Large animal facility within an academic hospital. ANIMAL(S): Thirty New Zealand White adult female rabbits (2.2-3.0 kg). INTERVENTION(S): Administration of 11 doses (one preoperative and 10 postoperative) of oral sunitinib (10 mg/kg/d) or placebo. MAIN OUTCOME MEASURE(S): Effect of short-term postoperative sunitinib administration on reproductive function after surgical uterine abrasion. RESULT(S): All animals were impregnated and survived until designated euthanasia. Sunitinib-treated animals had a larger average litter size (7.7 ± 1.9 vs. 5.6 ± 2.7 kits) and offspring viability (7.1 ± 2.7 vs. 3.5 ± 3.2 kits) compared with placebo-treated animals. There was no difference in gestational length or aberration in the maintenance of fertility. There were no gross abnormalities, detectable birth defects, or growth disparity in offspring from sunitinib versus placebo-treated mothers. The adhesion burden identified at euthanasia after parturition was lower in sunitinib compared with placebo-treated animals (N = 10/group). CONCLUSION(S): Sunitinib ameliorated adhesion-induced reproductive aberrations after surgical uterine abrasion and may be an efficacious strategy to reduce postoperative pelvic adhesions.
OBJECTIVE: To determine the effect of sunitinib (Sutent; SU11248; Pfizer), a US Food and Drug Administration-approved receptor tyrosine kinase inhibitor previously shown to reduce de novo pelvic adhesion formation, on reproductive function after surgical uterine abrasion in a rabbit model. DESIGN: Randomized placebo-controlled study. SETTING: Large animal facility within an academic hospital. ANIMAL(S): Thirty New Zealand White adult female rabbits (2.2-3.0 kg). INTERVENTION(S): Administration of 11 doses (one preoperative and 10 postoperative) of oral sunitinib (10 mg/kg/d) or placebo. MAIN OUTCOME MEASURE(S): Effect of short-term postoperative sunitinib administration on reproductive function after surgical uterine abrasion. RESULT(S): All animals were impregnated and survived until designated euthanasia. Sunitinib-treated animals had a larger average litter size (7.7 ± 1.9 vs. 5.6 ± 2.7 kits) and offspring viability (7.1 ± 2.7 vs. 3.5 ± 3.2 kits) compared with placebo-treated animals. There was no difference in gestational length or aberration in the maintenance of fertility. There were no gross abnormalities, detectable birth defects, or growth disparity in offspring from sunitinib versus placebo-treated mothers. The adhesion burden identified at euthanasia after parturition was lower in sunitinib compared with placebo-treated animals (N = 10/group). CONCLUSION(S): Sunitinib ameliorated adhesion-induced reproductive aberrations after surgical uterine abrasion and may be an efficacious strategy to reduce postoperative pelvic adhesions.
Authors: Agnieszka Karbownik; Edyta Szałek; Katarzyna Sobańska; Wojciech Połom; Tomasz Grabowski; Anna Biczysko-Murawa; Marcin Matuszewski; Anna Wolc; Edmund Grześkowiak Journal: Eur J Drug Metab Pharmacokinet Date: 2014-03-28 Impact factor: 2.441