PLASMA HYDROXY-METRONIDAZOLE METRONIDAZOLE RATIO IN PATIENTS WITH LIVER-DISEASE AND IN HEALTHY-VOLUNTEERS/

Metronidazole pharmacokinetics were studied in patients with different degrees of liver cirrhosis, classified according to the Child-Pugh al gorithm (A, B or C, as liver disease severity increases) and in schist osomic patients. Metronidazole (500 mg) was administered i.v, as a slo w infusion over 20 min, and blood samples were collected at set interv als after the end of the infusion. The plasma concentrations of metron idazole and its main metabolite hydroxy-metronidazole were quantified by reversed-phase h.p.l.c, with u.v, detection, The metronidazole and hydroxy-metronidazole areas under the curve from 0 to 24 h (AUC0,24h), the metronidazole terminal elimination half-life (t(1/2)), the total clearance (CL), the metronidazole volume of distribution (V) values an d the hydroxy-metronidazole/metronidazole concentration ratios as a fu nction of time were calculated for each group. Comparison of the metro nidazole AUC0,24h, t(1/2) and CL values revealed that metronidazole me tabolism is progressively impaired as the severity of liver disease in creases, There were no variations in these parameters between the schi stosomic and Child-Pugh A groups, In addition, there were no differenc es in the V and hydroxy-metronidazole AUC0,24h among the various group s studied. However, metronidazole metabolism was delayed in patients w ith hepatic disease, as illustrated by the hydroxy-metronidazole/metro nidazole ratio 10 min after the end of metronidazole infusion, These r esults indicate that the clinical assessment of liver disease is paral leled by an impairment of metronidazole metabolism. Of the studied var iables, we propose the hydroxy-metronidazole/metronidazole ratio 10 mi n after metronidazole infusion as a suitable and practical index for l iver function evaluation.