Journal Information
Vol. 32. Issue 2.
Pages 77-82 (January 2008)
Vol. 32. Issue 2.
Pages 77-82 (January 2008)
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The Pharmacokinetics of Metronidazole and Gentamicin in a Single Preoperative Dose as Antibiotic Prophylaxis in Colorectal Surgery
Farmacocinética del metronidazol y la gentamicina en dosis única preoperatoria para profilaxis antibiótica quirúrgica en cirugía colorrectal
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José Manuel Ventura Cerdáa,
Corresponding author
ventura_jma@gva.es

Correspondence: Servicio de Farmacia. Hospital General de Castellón. Avda. Benicasim, s/n. 12004 Castellón. España.
, Manuel Alós Almiñanaa, Jesús Nomdedeu Guinotb, Virginia Merino Sanjuánc, José Luis Salvador Sanchísb
a Servicio de Farmacia, Hospital General de Castellón, Castellón, Spain
b Servicio de Cirugía General y Digestiva, Hospital General de Castellón, Castellón, Spain
c Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Valencia, Valencia, Spain
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Abstract
Objective

To describe, in patients undergoing colorectal surgery (CRS), the pharmacokinetics of a single, prophylactic preoperative dose of 1500mg of metronidazole plus 240mg gentamicin and measure its efficacy in accordance with the accepted pharmacodynamic and microbiological parameters.

Method

Thirty-six patients undergoing CRS agreed to participate in the study. Three blood samples were taken from each. Cmax 15 minutes after finishing the infusion of the mixture, CfinIQ on finishing the surgery, and Cmin between 12 and 24 hours post-administration. The concentrations of metronidazole and gentamicin in each simple were measured and the pharmacokinetic parameters were estimated (dV-distribution volume, Cl-plasma clearance). For the metronidazole, concentrations in excess of 8μg/mL were considered effective, and for gentamicin, Cmax in excess of 9μg/mL and inhibition quotients above 8.

Results

All the concentrations of metronidazole, both CmaxMTZ and CfinIQMTZ were above 8μg/mL and all the CmaxGEN in excess of 9μg/mL. The ClGEN was 13.8 (3.8), with no individual value below 8. For the metronidazole, a dV of 0.68 (0.2)L/kg was estimated and a Cl of 3.15 (1.20)L/h and for the gentamicin, the dV as 0.23 (0.06)L/kg and the Cl was 4.71 (1.95)L/h.

Conclusion

In patients undergoing CRS, surgical intervention did not significantly modify the pharmacokinetics of metronidazole or gentamicin in comparison with other groups of patients. The prophylaxis using a single, pre-surgical dose enables the achievement, for both antimicrobial agents, concentrations of a sufficient size to guarantee clinical efficacy.

Key words:
Antibiotic prophylaxis
Colorectal surgery
Pharmacokinetics
Metronidazole
Gentamicins
Resumen
Objetivo

Describir, en pacientes sometidos a cirugía colorrectal (CCR), la farmacocinética de una dosis única preoperatoria de metronidazol 1.500mg más gentamicina 240mg como pauta profiláctica, y estimar su efectividad de acuerdo con parámetros subrogados farmacodinámicos y microbiológicos.

Método

Treinta y seis pacientes sometidos a CCR aceptaron su participación en el estudio. De cada uno de ellos se tomaron tres muestras de sangre: Cmáx, 15min tras finalizar la infusión de la mezcla, CfinIQ al finalizar la cirugía, y Cmín entre las 12 y 24h posteriores a la administración. Se determinaron las concentraciones de metronidazol y gentamicina en cada muestra y se estimaron los parámetros farmacocinéticos (Vd: volumen de distribución, Cl: aclaramiento plasmático). Para el metronidazol, se consideraron efectivas concentraciones superiores a 8μg/ml, y para la gentamicina, Cmáx superiores a 9μg/ml y cocientes de inhibición superiores a 8.

Resultados

Todas las concentraciones de metronidazol, tanto CmáxMTZ como CfinIQMTZ fueron superiores a 8μg/ml, y todas las CmáxGEN, superiores a 9μg/ml. El CIGEN fue de 13,8±3,8, con ningún valor individual inferior a 8. Para el metronidazol, se estimó un Vd de 0,68±0,2l/kg y un Cl de 3,15±1,20l/h, y para la gentamicina, el Vd fue de 0,23±0,06l/kg, y el Cl, de 4,71±1,95l/h.

Conclusión

En pacientes sometidos a CCR la intervención quirúrgica no modifica significativamente la farmacocinética del metronidazol y la gentamicina respecto a otros grupos de pacientes. La profilaxis en dosis única prequirúrgica permite alcanzar, para ambos antimicrobianos, concentraciones de magnitud suficiente para garantizar su efectividad clínica.

Palabras clave:
Profilaxis antibiótica
Cirugía colorrectal
Farmacocinética
Metronidazol
Gentamicina
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