Effect of gamma-irradiation on disposition of the local anaesthetic, carbisocaine in rabbits.
14C Labelled carbisocaine, a local anaesthetic agent, has been administered intravenously in a dose of 2 mg kg-1 to rabbits 7 days after whole-body 60Co gamma-irradiation with a dose of 5 Gy (1.9 Gy min-1) and to control rabbits. The plasma carbisocaine concentration-time courses were approximated by biexponential equations. The estimated pharmacokinetic parameters obtained when the data were fitted to an open two-compartment model were significantly different for the irradiated group relative to control animals, indicating a radiation-induced slower elimination rate of carbisocaine: AUC: 0.37 vs 0.29% dose min mL-1, CLtot: 109.8 vs 155.4 mL min-1, Vdss: 27.6 vs 33.2 mL kg-1, kel: 0.0259 vs 0.0307 min-1, MRT: 251.7 vs 214.6 min. The total excreted amount of 14C radioactivity in the irradiated group was lower in comparison with controls: 6.5 vs 8.7% in bile and 18.3 vs 23.7% in urine. However, lower carbisocaine concentrations were recorded in the heart, lungs, liver, and kidneys of irradiated rabbits compared with controls.
Kállay
Z
Z
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
Durisová
M
M
Trnovec
T
T
Svoboda
V
V
D000779:Anesthetics, Local / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D002219:Carbamates / Q000097:blood / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D005720:Gamma Rays; D007275:Injections, Intravenous; D011817:Rabbits; D014018:Tissue Distribution; D014916:Whole-Body Irradiation
D000779:Anesthetics, Local; D002219:Carbamates; D002250:Carbon Radioisotopes; C046030:carbizocaine