Parámetros farmacocinéticos de gentamicina en recién nacidos de término: ¿Es necesario monitorizar en forma sistemática sus concentraciones plasmáticas? / Gentamicin pharmacokinetics in term newborn: ¿Is it necessary to systematically monitor plasmatic levels?

Background: Gentamicin is indicated as empiric treatment for neonatal sepsis. Plasmatic levels dosification of gentamicin is a common practice. The relationship between peak plasma concentration (Cmáx) with minimum inhibitory concentration (MIC) (Cmáx/MIC) is the parameter that best predicts treatment efficacy. Aim: To determine pharmacokinetics of gentamicin in term newborn infants. Methods: Term newborn infants receiving gentamicin, without critical illness in which plasmatic levels of gentamicin was performed were included. Elimination clearance (Cl) elimination half-life (t½) and volume of distribution (Vd) were calculated. In each case the value of Cmax/MIC parameter was calculated, considering a MIC value of 1 μg/mL for Escherichia coli. Results: Thirteen newborns were included. The mean PK values were Cl: 0.26 mL/hour, Vd: 0.54 L/kg and t½: 6.8 h. Cmax/MIC was > 8 in 6 newborns. Conclusions: Pharmacokinetic parameters of gentamicin are predictable in term newborn infants. With gentamicin doses normally used Cmax/MIC values reached 8 in 6 newborns. It is necessary to review the usefulness of plasma drug monitoring and gentamicin dosage in this group of newborns.

Introducción: Gentamicina es utilizada como tratamiento empírico en la sepsis neonatal. El monitoreo de su concentración plasmática es una práctica frecuente. La relación entre la concentración plasmática máxima (Cmax) y la concentración inhibitoria mínima (Cmax/ CIM) es el parámetro que mejor predice la eficacia. Objetivo: Determinar los parámetros farmacocinéticos (FC) de gentamicina en recién nacidos (RN) de termino. Material y Métodos: Se incluyeron RN de término, sin enfermedad crítica, en tratamiento con gentamicina (4 mg/kg/24 h) en los que se realizó monitoreo de su concentración plasmática. Se determinaron: clearence de eliminación (Cl), vida media de eliminación (t½) y volumen de distribución (Vd). Se estimó la Cmax/CIM, considerando una CIM de 1 μg/mL para Escherichia coli. Resultados: Participaron 13 RN. La media de Cmax fue 8,19 μg/mL y de Cmin 0,73 μg/mL. La media de los parámetros farmacocinéticos fue: Cl 0,26 mL/h, Vd 0,54 L/kg, t½ 6,8 h. La razón Cmáx/CIM fue ≥ 8 en 6 de los 13 RN. Conclusiones: Los parámetros FC de gentamicina en RN de término, sin enfermedad crítica, son predecibles. La posología habitual no permitió obtener valores de Cmax/CIM > 8 en todos los casos. Es necesario revisar la necesidad de monitorizar su concentración plasmática en forma sistemática y la posología de gentamicina en este grupo de pacientes.

Clinical pharmacokinetics of gentamicin. Estimation of initial dosing parameters in hospitalized patients at Al-Amiri Hospital Kuwait

The objectives of this study were to: [1] derive equations for estimating gentamicin clearance [Clgent] and volume of distribution [Vd] based on the local population attending Al-Amiri Hospital, Kuwait; [2] independently evaluate these equations by comparison with other published methods in their predictive ability to estimate Clgent and Vd. Clgent and Vd were calculated in 47 patients [group 1] using the Sawchuk-Zaske method. Regression analysis was used to derive a correlation between creatinine clearance [Clcr] and Clgent, Vd and actual body weight [ABW]. Based on actual Clgent and Vd values, the predictive ability of the estimated parameters from the regression equations was validated and compared with 4 published methods using mean error [ME], i.e. bias, and mean squared error [MSE] and root mean squared error [RMSE], i.e. precision. All equations were also evaluated in an independent second group [group 2] of 23 patients. The mean +/- SD values of Clgent and Vd were 4.0 +/- 1.8 lúh-1 and 16.8 +/- 6.7 liters, respectively. The derived equations were: Clgent = [0.760] [Clcr] + 1.117 [r = 0.701] and Vd = [0.165] [ABW] + 5.604 [r = 0.532]. In comparison to the 4 published methods, the derived equations were less biased [ME = 0.00] and more precise [MSE = 1.68, RMSE = 1.02] in predicting Clgent [p < 0.05], and less biased [ME = -0.01] with no difference in precision [MSE = 36.22, RMSE = 4.59] in predicting Vd [p > 0.05]. This precision was confirmed in the second group of 23 patients, where the derived equations were less biased [ME = -0.1] and more precise [MSE = 3.22, RMSE = 1.48] in predicting Clgent [p < 0.05], whilst no difference was found for prediction of Vd [p > 0.05]. The equations developed in this study provided a reliable estimation of Clgent and Vd. It is planned to use them at Kuwait Hospitals to help provide more individualized patient dosing information to physicians

Acumulación temprana de gentamicina en el suero de pacientes cancerosos con insuficiencia renal / Accumulation of serum gentamicin levels of cancer patients with renal impairment

Se realizó la cuantificación de gentamicina en el suero, dos horas después de la aplicación, en 11 pacientes cancerosos (seis con función renal y cinco con insuficiencia renal). Se utilizó el método inmunoenzimático EMIT. Los enfermos con función renal normal mostraron concentraciones de gentamicina que variaron entre 1.75 y 3.85 ug/ml de suero y una media de 2.5 ñ 0.8 de desviación estándar (DE), mientras que en los pacientes con insuficiencia renal los valores fluctuaron entre 2.25 y 10.00 ug/ml de suero y promediaron 5.3 ñ 3.2 de DE. El análisis estadístico mostró que existen diferencias significativas entre ambos grupos p < 0.01. Aparentemente la cuantificación de gentamicina en el suero, desde el inicio del tratamiento de pacientes con insuficiencia renal, parece ser el estudio de laboratorio más confiable para evitar que se produzcan lesiones renales más severas en estos enfermos. Por otro lado, cuatro de las seis pacientes con función renal normal mostraron buena respuesta al tratamiento con gentamicina, mientras que ninguna de las cinco pacientes con insuficiencia renal respondió de manera adecuada a este mismo tipo de tratamiento.

Simultaneous monitoring of amikacin and gentamycin levels in plasma versus prostatic fluid can predict thir in vivo therapeutic efficacy in chronic bacterial prostatitis

The study was conducted on 20 chronic bacterial prostatitis patients, they were divided into amikacin and gentamycin groups. They received therapeutic doses of i.m. twice daily amikacin and gentamycin. Their peak drug levels and pH measurements in plasma versus prostatic secretion were assessed after the first and last dose of the 7-day course together with post therapeutic bacteriological assessment. Results revealed a positive correlation between beneficial levels of the two aminoglycosides recovered in the prostatic fluid and the absence of bacterial growth in post therapeutic specimens. No definite relationship was correlated between drug levels and pH measurements in prostatic secretion. Therefore, performing initial quantitative detection of peak levels of aminoglycosides in the expressed prostatic secretion after the first dose was recommended, to determine whether the drugs are recovered in beneficial levels. So, the physician could take early decision whether to continue the course or to cut it short when the therapeutic value is not worth the hazards, costs and disappointment of inadequate response

Monitoreo de antibioticos / Antibiotic monitoring

Se estudiaron los niveles séricos de aminoglucósidos y cloramfenicol en 67 enfermos con infecciones severas. Se realizaron 114 determinaciones mediante el método microbiológico. El control interno de calidad demonstró una exactitud (límite de confiabilidad 95%) de 22,4%. Los resultados obtenidos indujeron a modificar la dosis unitaria en 29 casos y el intervalo de administración en 12 enfermos. En total, de 61,2% de los enfermos requirieron modificaciones en la posología pese al uso de un monogramo y/o programa de ajuste de dosis (Hewlett-Packard 01784D y 01785D

Monitorizaçäo dos níveis séricos da gentamicina: implicaçöes e relevância em antibioticoterapia / Monitoring of serum levels of gentamicin: implications and significance in antibiotic therapy

A concentraçäo sérica da gentamicina foi determinada, através de RIE, em 83 pacientes de um hospital geral. Os pacientes foram subdivididos em 2 grupos, segundo as características da funçäo renal. O intervalo entre as doses do antibiótico foi aumentado nos pacientes com insuficiência renal, com base nos valores plasmáticos de creatinina ou da DCE. Observou-se, em aproximadamente 50% dos pacientes de qualquer dos grupos considerados, que os níveis séricos de gentamicina estavam acima ou muito abaixo dos valores considerados terapêuticos. Portanto, para evitar näo só os níveis elevados, potencialmente tóxicos, como também os níveis subterapêuticos, é importante, se näo obrigatória, a determinaçäo sérica da gentamicina, ao longo do tratamento, indicaçäo essa que se afigura mais evidente para os pacientes de maior risco e naqueles com insuficiência renal