萘丁美酮代谢物MNAA对人尿褪黑素水平的影响

Effects of elimination rate of active metabolite MNAA of nabumetone on the levels of melatonin (MT) in male urine

采用高效液相荧光法（ｅｘλ＝２９５ｕｍ，ｅｍλ＝３４０ｎｍ）同步检测人尿中萘丁美酮（ＮＡＢ）的主要代谢物６－甲氧基－２－萘乙酸（ＭＮＡＡ）及褪黑素（ＭＴ）。５名男性志愿者于１８点口服５００ｍｇＮＡＢ后，尿中ＭＴ累积量仍呈昼夜变化节律，其累积量分别从未服药前的每１２小时２７４．０±５８ｐｍｏｌ（夜晚）和７７．６±２５ｐｍｏｌ（白天）减少至１４５．６±３２ｐｍｏｌ（夜晚）和５０．３±１２ｐｍｏｌ（白天）（Ｐ值均小于０．０１）。依照尿中的ＭＮＡＡ消除速率对中点时间作曲线，求得ＭＮＡＡＴ为２２．５ｈ，ＴＰＫ为１４．２ｈ，与已知报告的血浆中数值相近。相关分析证明，ＭＴ累积量抑制与ＭＮＡＡ消除速率相关（ｒ＝０．９６４４，Ｐ＜０．０５）。ＭＮＡＡ在尿中９６ｈ的累积量仅占口服５００ｍｇＮＡＢ的３．５％，高于ＨａｄｄｏｃｋＲＥ采用同位素得出１％的结论。

The main metabolite of nabumetone(NAB),the 6-methoxy-2-naphthylacetic acid(MNAA),the potent inhibitor of PGs,and physiological secretion of MT in male urine were determinated by HPLC with fluorometric detector(λex=295nm,λem=340nm).The results were shown that after p.o.NAB.at 1800o'clock,the circadian variation of MT levels were still undergoing the nocturnal increase,but the accumulated amount of MT in 5 health male urine were reduced from274±58 pmol/12h (N)and 77.6±25 pmol/12h(D)to 145.6 ±32 pmol/12 h,50.3± 12 pmol/12 h respectively.Accounting to the curve of elimination rate vs the middle time, we got the TPK=14.2hr that were close to the value in plasma.The regression analysis was shown that the inhibition degree of MT was correlated to the elimination rate of MNAA.(r=0.9644,P<0.05).The accumulated amount of free MNAA during 96 hr in urine was accounting for 3.5% dose of 500 mg NAB.higher than 1.0% reported by Haddock R.E.using isotope. We suppose that even if MNAA does not structurally resemble MT or indomethacin,but it still might interrupt MT synthesls via PGs.