Okereke C S, Abdel-Rhaman M S, Friedman M A
Department of Pharmacology and Toxicology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark 07103-2714.
Toxicol Lett. 1994 Aug;73(2):113-22. doi: 10.1016/0378-4274(94)90101-5.
Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, BZ-3) is a UV absorber that is used extensively in medicine, cosmetics and industry as a sunscreen and color fastener. Exposure to the chemical is through the dermal and oral route. Bioavailability of the chemical absorbed through the skin is different from that seen through the oral route. The disposition of BZ-3 was investigated after dermal administration of 100 mg/kg body weight (body wt.) in Sprague-Dawley rats. Blood samples were collected at various intervals and the parent compound and its metabolites were analyzed by HPLC. Absorption was rapid as the parent compound and its metabolites were detected in plasma 5 min post-administration. The half-life (t1/2) of absorption was 3.45 h corresponding to an absorption rate constant of 0.2 h-1. Peak plasma concentration of 35 +/- 4.5 micrograms/ml (mean +/- standard error of the mean, S.E.) was attained at 2.5 h post-administration. Disappearance from the plasma was biphasic with different half-lives (1.3 for alpha phase and 15.05 h. for beta phase), the area under the plasma concentration versus time curve was 211.1 +/- 38.2 micrograms/ml/h (mean +/- S.E). There was also extensive binding of BZ-3 and its metabolites to plasma proteins. Three metabolites were identified in plasma, 2,4-dihydroxybenzophenone (DHB) and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB) were the major metabolites detected in the plasma, while 2,3,4-trihydroxybenzophenone (THB) was detected in trace amounts. Tissue distribution studies revealed that THB was the major metabolite followed by DHB (both free and conjugated) in all tissues examined. The liver contained the highest amount followed by the kidney, spleen and testes, respectively.
二苯甲酮-3（2-羟基-4-甲氧基二苯甲酮，BZ-3）是一种紫外线吸收剂，在医药、化妆品和工业中广泛用作防晒剂和固色剂。接触该化学物质的途径为经皮和口服。经皮肤吸收的该化学物质的生物利用度与经口服途径吸收的情况不同。在体重为100mg/kg的Sprague-Dawley大鼠经皮给药后，对BZ-3的处置情况进行了研究。在不同时间间隔采集血样，通过高效液相色谱法分析母体化合物及其代谢产物。给药后5分钟血浆中就检测到母体化合物及其代谢产物，吸收迅速。吸收的半衰期（t1/2）为3.45小时，吸收速率常数为0.2 h-1。给药后2.5小时达到血浆峰值浓度35±4.5微克/毫升（平均值±平均标准误差，S.E.）。血浆中药物的消除呈双相，半衰期不同（α相为1.3小时，β相为15.05小时），血浆浓度-时间曲线下面积为211.1±38.2微克/毫升/小时（平均值±S.E.）。BZ-3及其代谢产物与血浆蛋白也有广泛结合。血浆中鉴定出三种代谢产物，2,4-二羟基二苯甲酮（DHB）和2,2'-二羟基-4-甲氧基二苯甲酮（DHMB）是血浆中检测到的主要代谢产物，而2,3,4-三羟基二苯甲酮（THB）仅微量检出。组织分布研究表明，在所检查的所有组织中，THB是主要代谢产物，其次是DHB（游离型和结合型）。肝脏中含量最高，其次分别是肾脏、脾脏和睾丸。
