Assay of metyrapone, metyrapol and the isomeric mono-N-oxides of metyrapone in biological fluids by high-performance liquid chromatography

Oral pharmacokinetics and in-vitro metabolism of metyrapone in male rats

“…The present oral pharmacokinetics study of MP in Wistar rats showed that MPOL, MP NOII and MPOL NOII were observed in plasma (Figure ), and MPOL NOI was also detected in urine (Figure ). The previous studies using SD female rats are reported that the five MP metabolites were detected in urine after an intraperitoneal administration and that MP was metabolized to MPOL, MP NOI and MP NOII in the liver microsomal fraction and to MPOL in the liver cytosolic fraction . Thus, strain specificity between Wistar and SD rats was observed in the production of the metabolites in the liver subcellular fractions and urine.…”

“…In our previous report, the MP metabolite was determined to be only MPOL by HPLC‐UV method used. Five metabolites of MP have been determined by HPLC‐UV, but the separation was not clean. In this study, we separated the peaks corresponding to MP, its five metabolites and IS without overlapping of the peaks in all of the biological samples tested (Figure ).…”

“…Using the developed method, we showed that MP was rapidly eliminated in plasma ( t 1/2 : 0.99 h) and that after its rapid absorption (Figure , Table ), negligible amounts were excreted in urine (Figure ). The renal excretion of MP seems to be the primary route of elimination following a single oral and intraperitoneal administration of MP to humans and SD male rats, respectively. On the other hand, the plasma concentrations of MPOL (the major metabolite), MP NOII and MPOL NOII increased rapidly after dosing (Figure ).…”

“…Although MP is used clinically, our knowledge of its pharmacokinetics in experimental animals remains quite limited. In the studies of the effects of administration on MP to rats, male Sprague Dawley (SD) rats received either a single intravenous or intraperitoneal injections of MP . In the case of intravenous administration, the plasma concentration of MP was reported to decrease rapidly and that of MPOL immediately increased.…”

“…To clarify the pharmacokinetic characteristics of MP, we needed to develop method for the simultaneous determination of MP and its five metabolites, because our previous determination involved only the determination of MPOL and the methodology reported by Usansky JI et al . did not permit all the metabolites to be completely separated …”