酸性成纤维细胞生长因子经皮给药创面面积及剂量对其血药浓度的影响

The effect of wound area and dosage acting on blood level of rhaFGF by transdermal delivery

目的:通过建立动物灼伤模型,采用125I?标记的酸性成纤维细胞生长因子(rhaFGF)结合TCA沉淀法,测家兔皮肤创面用药后血清的总放射活性、TCA可沉淀放射性浓度,比较面积和剂量对局部用药的全身吸收的影响,探讨rhaFGF局部用药的安全性。方法:运用NS-FⅡ型多功能光谱治疗仪器建立微波灼伤动物模型;用Iodogen法标记rhaFGF;根据药理学量效关系原则,分析血清总放射性和TCA沉淀部分放射性浓度。结果:(1)家兔烧伤创面给药全身吸收的生物利用度较低。小剂量小面积组血清总放射性和TCA沉淀部分放射性浓度的绝对生物利用度分别为4.8%和7.9%。小剂量大面积组为3.2%和5.2%;大剂量小面积组为3.2%和6.2%;大剂量大面积组为0.9%和1.9%。剂量和烧伤创面大小对125I-rhaFGF的全身吸收无明显影响(P>0.05)。(2)多次给药组第5次给药后的生物利用度为3.1%和11.2%,与第1次给药(3.2%和6.2%)相比无统计学意义(P>0.05)。(3)分别经烧伤创面和静脉给予相同剂量125I-rh aFGF(195kBq)后,前者的血清总放射性和TCA酸沉淀放射性在12h前明显低于后者(P<0.01或P<0.05),12h后两者差别无统计意义(P>0.05)。结论:给药剂量和烧伤创面对125I-rhaFGF的全身吸收无明显影响,rhaFGF多次重复大面积经皮给药安全可靠。

OBJECTIVE To study the effects of differem doses and burn wound sizes on systemic absorption of ^125-I-rhaFGFr. METHODS An animal model of microwave-burnt wound was established by NS-FⅡ multifunction spectrum therapeutics equipment, which was divided into six groups,including： the group of small area with minute dose;small area with flushing dose; large area with minute dose; large area with flushing dose; small area with multiple dose; and small area with intravenous dose. Test the gross blood serum radioactivity and the radioactive concentration-time change of TCA sediment. RESULTS （1） The bioavailability of systemic absorption in rabbit＇s burn wound was low by transdermal delivery. In the group of small area with minute dose, absolute bioavailability of the gross blood serum radioactivity and the radioactive concentration for TCA sediment are 4. 8% and 7. 9%. While in the group of small area with flushing dose, the data wad 3. 2% and 5. 2%; in the group of large area with minute dose, the data was 3. 2% and 6. 2% ;and in the group of large area with flushing dose, the data was 0. 9% and 1.9% ; the effect of systemic absorption for ^125 I-rhaFGF by wound area and dosage was not obvious（P〉0. 05）. （2） In the group of small area with multiple dose, the bioavailability after the fifth administration was 3. 1% and 11.2%. Compared with the first administration （the bioavailability was 3. 2% and 6. 2%）, there was no obvious statistical difference （P〉0. 05）. （3） While giving the same dosage of ^125-rh aFGF（195kI3q） through bum wound and vein independently, the gross blood serum radioactivity and the radioactivity of TCA sediment was obvious lower in the former team than the latter （P〈0. 01 or P〈0. 05）. However, there is no difference between them after 12 hours（P〉0. 05）. CONCLUSION There is no obvious influence on systemic absorption of ^125 I-rhaFGF by wound area and dosage, and it is safe to repeat administration per cutem of the rhaFGF in large area.