Prevention of chemotherapy-induced intraperitoneal adhesion formation in rats by icodextrin at a range of concentrations.
OBJECTIVE
Two controlled in vivo studies in rats have investigated the effect of icodextrin solution on intraperitoneal chemotherapy-induced adhesion formation. The first study evaluated the effect of three concentrations of icodextrin (4, 15, 20% w/v) in comparison to a phosphate-buffered saline (PBS) control in response to intraperitoneal doxorubicin (n = 40). The second study compared the effect of 4% icodextrin to Ringers' lactate solution (RLS) control in response to intraperitoneal bleomycin (n = 30).


METHODS
Doxorubicin and bleomycin were administered via a continuous pump and as a single bolus (bleomycin only). Doxorubicin 2 ml (23.2 microg/ml) was delivered via pump in conjunction with 20 ml of 4, 15, or 20% icodextrin or PBS (n = 10 per group). In the bleomycin experiments rats received either 2 ml (0.77 U/ml) bleomycin delivered via pump in conjunction with 15 ml 4% icodextrin or RLS, or 0.77 or 0.077 U bleomycin delivered in 15 ml 4% icodextrin or RLS administered as a bolus injection (n = 5 per group). Seven days after the initiation of doxorubicin treatment and 9 days after initiation of bleomycin treatment, the rats were euthanized by CO(2) and the extent of peritoneal adhesion formation was evaluated using an 8-point scoring system.


RESULTS
When icodextrin was administered in conjunction with doxorubicin there was a reduction in the formation of adhesions compared to PBS. Efficacy increased with the concentration of icodextrin used. The lowest dose of bleomycin (0.077 U) caused very few adhesions. Results with bleomycin 0.77 U/ml (pump) and 0.77 U (bolus) showed that 4% icodextrin was significantly more effective than RLS at preventing adhesion formation, irrespective of the dosing regimen.


CONCLUSIONS
These studies suggest that 4% icodextrin may reduce adhesion formation caused by intraperitoneal chemotherapy.
Conroy
Susan E
SE
ML Laboratories PLC, St Albans, AL1 3HW, Hertfordshire, UK. sueconroy@aol.com
Baines
Laura
L
Rodgers
Kathleen
K
Deviren
Figen
F
Verco
Shelagh J
SJ
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005936:Glucans / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D000077607:Icodextrin; D007263:Infusions, Parenteral; D010532:Peritoneal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000139:chemically induced / Q000517:prevention & control*
D000970:Antineoplastic Agents; D005936:Glucans; D001761:Bleomycin; D000077607:Icodextrin; D004317:Doxorubicin; D005947:Glucose