Hansson G
Prostaglandins. 1979 Nov;18(5):745-71. doi: 10.1016/0090-6980(79)90095-9.
The metabolism of the prostaglandin F2 alpha analogues, 15-methyl-delta 4-cis-PGF1 alpha and 16,16-dimethyl-delta 4-cis-PGF1 alpha, has been investigated in the cynomologus monkey and the human female. The two analogues, tritium labelled in the 9 beta-position, were administered by intramuscular injections into the monkeys and by subcutaneous injections into the human. Excretion of tritium labelled products were followed in urine (in both species) and feces (in monkeys only) and several metabolites were identified by GC/MS. The analogues were found to be resistant to the 15-hydroxy dehydrogenase and furthermore the degradation by beta-oxidation was delayed. About 13% of the given dose of 15-methyl-delta 4-cis-PGF1 alpha was excreted unchanged into urine and feces from the monkey. The corresponding figure for 16,16-dimethyl-delta 4-cis-PGF1 alpha was about 20%. In addition, a large part of the metabolites had the carbon skeleton intact and were only metabolized by omega-oxidation. The relative resistance to degradation of these two analogues is likely to be the basis for their prolonged pharmacological activity.
已在食蟹猴和人类女性中研究了前列腺素F2α类似物15-甲基-δ4-顺式-PGF1α和16,16-二甲基-δ4-顺式-PGF1α的代谢情况。这两种在9β位用氚标记的类似物，通过肌肉注射给予猴子，通过皮下注射给予人类。对尿液（两种物种）和粪便（仅猴子）中的氚标记产物排泄情况进行了跟踪，并通过气相色谱/质谱法鉴定了几种代谢物。发现这些类似物对15-羟基脱氢酶具有抗性，而且β-氧化降解也有所延迟。给予猴子的15-甲基-δ4-顺式-PGF1α剂量中约13%以原形排泄到尿液和粪便中。16,16-二甲基-δ4-顺式-PGF1α的相应数字约为20%。此外，大部分代谢物的碳骨架保持完整，仅通过ω-氧化进行代谢。这两种类似物相对抗降解的特性可能是其药理活性延长的基础。
