The Dynamic Observation Of 5-FU Concentration In Regional Lymphatic Nodes And Local Tissue With Continuous Intr-arterial Infusion

[Objective]①We investigated 5-FU concentration in tongue, the regional lymph nodes and pharmacokinetics with superficial temporal artery retrograde intubation for lingual artery continuous intraarterial and femoral vein infusion therapy in order to find a effective way for neoadjuvant chemotheapy for oral caner.[Methods]①Sixteen healthy dogs of the study, they were divided at random into two groups:A (superficial temporal artery retrograde intubation group) and B (femoral vein infusion group). Continuous infusion 5-FU through the superficial temporal artery or femoral vein for 24h. At different time points in A, B group contralateral jugular vein and femoral venous collected plasma samples. To take the dogs of the A group ipsilateral body of tongue, ipsilateral root of tongue, ipsilatera submandibular lymphatic nodes, contralateral boay of tongue,contralateral root of tongue, contralateral submandibular lymphatic nodes. To take the dogs of the B group body of tongue, root of tongue, submandibular lymphatic nodes in 12h and 24h.②The concentration of 5-FU in plasma and tissue at different times were determined by PR-HPLC. Analyses were carried out on an Agilent HC-C18C18(150 mm×4.9 mm,5μm PN,588925-902);column at 30℃, eluted with a mobile phase consisting of methanol-water(95:5) and detected at 256 nm. The flow rate was 1.0 ml·min-1.③The concentration-time data were processed with DAS(2.0) pharmacokinetic procedure. Compare with 5-FU concentration levels of plasma and tissues.[Results]①The healthy dogs with anesthesia can withstand the superficial temporal artery retrograde 5-FU to continue 24h and to maintain stable vital signs.②Their pharmacokinetics parameters with collected plasma samples of contralateral jugular vein were as follows:A (superficial temporal artery retrograde intubation group) Tmax (14±4.44)h, Cmax (565.35±82.62) mg·L-1; B (femoral vein infusion group) Tmax (16±4.52)h, Cmax (457.29±59.74) mg·L-1; The plasma concentration of A group higher than the B group in different time points (P<0.05). Their pharmacokinetics parameters with collected plasma samples of contralateral femoral vein were as follows:A (superficial temporal artery retrograde intubation group) Tmax (16±1.49)h, Cmax (391.52±67.14) mg·L-1; B (femoral vein infusion group). Tmax (23±8.24)h, Cmax (526.36±77.44) mg·L-1; The plasma concentration of A group higher than the B group after jugular vein 5-FU 2h, The plasma concentration of the B group higher than the A group after 2h to the end (P< 0.05).③The differences in drug concentration of superficial temporal artery infusion group were as follows:ipsilateral body of tongue[(405.18±42.07)μg·g-1] higher than ipsilateral root of tongue[(290.82±73.79)μg·g-1] (P=0.36); ipsilateral body of tongue higher than contralateral body of tongue[(102.96±11.85)μg·g-1] (P<0.01); ipsilateral root of tongue higher than ipsilateral root of tongue[(85.06±23.08)μg·g-1] (P=0.02); ipsilatera submandibular lymphatic nodes[(254.00±31.04)μg·g-1] higher than contralateral submandibular lymphatic nodes[(70.09±2.36)μg·g-1] (P<0.01). Compared with the femoral vein administration:ipsilateral submandibular lymphatic nodes of the superficial temporal artery retrograde intubation group drug concentration for the femoral vein retrograde group[(0.56±0.98)μg·g-1] 10 to 15 times (P<0.01), ipsilateral body of tongue of the superficial temporal artery retrograde intubation group higher than the body of tongue [(29.31±1.43)μg·g-1] of the femoral vein infusion group(P<0.01), ipsilateral root of tongue [(5.59±1.55)μg·g-1] of the superficial temporal artery retrograde intubation group higher than the root of tongue of the femoral vein infusion group (P<0.01)[Conclusion]①Dogs for the establishment of regional arterial retrograde continuous administration of animal models.②Through the superficial temporal artery retrograde intubation, head neck region 5-FU drug concentrations higher than femoral vein infusion; Through femoral vein infusion into the systemic circulation of the drug administration was significantly higher than of superficial temporal artery.③Ipsilateral tongue and ipsilatera submandibular lymphatic nodes of the superficial temporal artery retrograde intubation groups 5-FU drug concentrations higher than femoral vein infusion.