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新生儿光疗条件下锡原卟啉、锡中卟啉和二碘氘代锡卟啉的光毒性

Phototoxicity of tin protoporphyrin, tin mesoporphyrin, and tin diiododeuteroporphyrin under neonatal phototherapy conditions.

作者信息

Fort F L, Gold J

机构信息

Dept of Toxicology, Abbott Laboratories, Abbott Park, IL 60064.

出版信息

Pediatrics. 1989 Dec;84(6):1031-7.

PMID:2531365
Abstract

Tin metalloporphyrins are being considered as therapeutic agents for neonatal hyperbilirubinemia, and it is possible that concurrent exposure to phototherapy will occur during their use. Euthymic hairless guinea pigs, Crl:IAF(HA)BR, were given daily intraperitoneal injections of tin protoporphyrin (SnPP), tin mesoporphyrin (SnMP), or tin diiododeuteroporphyrin (SnI2DP) for 3 successive days. They were concurrently exposed to ambient light or two different kinds of phototherapy light under conditions similar to that found in neonatal intensive care units. Phototherapy light exposure was for a continuous period of approximately 72 hours following the first injection of metalloporphyrin. The presence or absence of phototoxicity under these conditions was determined by observations for an erythematous response on the back and ears of the guinea pigs. The dosages used were 0.75, 3.75, and 7.5 mg/kg per day of SnPP, 0.075, 0.375, and 0.75 mg/kg per day of SnMP, and 0.9, 4.5, and 9.0 mg/kg per day of SnI2DP. These dosages for each drug were approximately 1 times, 5 times, and 10 times, respectively, the maximum anticipated clinical dosage. At equal multiples of the clinical dosages, SnI2DP was less phototoxic than SnPP, and SnMP was the least phototoxic of the three compounds. SnPP was marginally phototoxic at the lowest dosage. SnMP was phototoxic only at the highest dosage under phototherapy light emitting ultraviolet A irradiation, but when phototherapy light not emitting ultraviolet A irradiation was used, SnMP was not phototoxic. In all cases, the phototoxic response was reversible when the drug and phototherapy treatment were discontinued.

摘要

锡金属卟啉正被视作治疗新生儿高胆红素血症的药物,在其使用过程中有可能同时接受光疗。将处于正常情绪状态的无毛豚鼠(品系为Crl:IAF(HA)BR)连续3天每天腹腔注射锡原卟啉(SnPP)、锡中卟啉(SnMP)或锡二碘代去氢卟啉(SnI2DP)。在类似于新生儿重症监护病房的条件下,它们同时暴露于自然光或两种不同的光疗光源下。在首次注射金属卟啉后,光疗光照持续约72小时。通过观察豚鼠背部和耳部的红斑反应来确定在这些条件下是否存在光毒性。所用剂量分别为:SnPP每天0.75、3.75和7.5毫克/千克;SnMP每天0.075、0.375和0.75毫克/千克;SnI2DP每天0.9、4.5和9.0毫克/千克。每种药物的这些剂量分别约为预期最大临床剂量的1倍、5倍和10倍。在临床剂量的同等倍数下,SnI2DP的光毒性低于SnPP,而SnMP是这三种化合物中光毒性最小的。SnPP在最低剂量时仅有轻微光毒性。SnMP仅在发射紫外线A的光疗光照下的最高剂量时具有光毒性,但当使用不发射紫外线A的光疗光照时,SnMP无光毒性。在所有情况下,当停止药物和光疗治疗时,光毒性反应是可逆的。

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