Efficacy of sustained-release radioprotective drugs in vivo.
In previous publications from this laboratory we suggested the use of radioprotective drugs in a sustained-release form as a practical way to cope with their high toxicity and quick metabolism and excretion. Cysteine and cysteamine, well-established radioprotectants, were used as model drugs and compressed at various concentrations (0-65%) into an insoluble tablet matrix, composed of ethylcellulose and stearic acid at various ratios and compression pressures. We demonstrated in vitro that when the release rate of the radioprotectants was measured under nitrogen, the kinetic data conformed with the Higuchi square root of time equation, indicating that the release of both drugs correlates with Higuchi's diffusional mechanism. In the present in vivo study, tablets containing cysteine or cysteamine in a slow-release matrix were implanted, into the stomachs of female rats. The rats were irradiated at various time intervals up to 12 h after implantation and their survival recorded daily. Utilizing a 1:3 ratio of ethylcellulose:stearic acid as a matrix, the protective effect of the drugs was remarkable eight hours after tablet implantation. The results reported indicate that slow-release tablet formulation is a possible method for delivering of radioprotective drugs over an extended period of time.
Shani
J
J
Department of Pharmacology, Hebrew University School of Pharmacy, Jerusalem, Israel.
Benita
S
S
Abdulrazik
M
M
Yerushalmi
A
A
D000818:Animals; D003543:Cysteamine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003545:Cysteine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D014916:Whole-Body Irradiation
D003692:Delayed-Action Preparations; D011837:Radiation-Protective Agents; D003543:Cysteamine; D003545:Cysteine