Pharmacokinetics of gentamicin during peritoneal dialysis in children.

Pharmacokinetics of gentamicin during peritoneal dialysis in children. The pharmacokinetics of gentamicin were examined on two occasions using intravenous and intraperitoneal routes in five children undergoing intermittent peritoneal dialysis for chronic renal failure. Serum, urine and dialysis fluid (DF) were assayed microbiologically for gentamicin and the data were subjected to computer analysis using equations evolved for a two-compartment model which considered the bi-directional flux of the drug. Following i.v. injection of 1 mg/kg of gentamicin, the apparent volume of distribution averaged 23% (range, 13 to 36%) of body wt (similar to normal), the mean half-life was 21hr (range, 9 to 37 hr; normal, 2 hr) and the peritoneal clearance averaged 4.0 ml/min/m 2 (range, 1.2 to 7.0 ml/min/m 2 ). During peritoneal administration of gentamicin (15 mg/liter of DF, 0.7 liters/m 2 administered in each cycle over 9 to 12 cycles), serum concentrations increased towards extrapolated steady-state levels which averaged 42% (range, 25 to 68%) of DF concentrations. The mean renal clearance of gentamicin was only 1.6 ml/min/m 2 while total body clearance ranged from 2.3 to 8.0 ml/min/m 2 , mostly occurring by a variable degree of dialysance. Peritoneal clearances and half-lives of gentamicin were similar in each patient following either treatment mode. The appreciable variability in gentamicin pharmacokinetics among adolescent patients with renal insufficiency necessitates dosage adjustments based on measurements of serum concentrations. Pharmacocinetique de la gentamycine au cours de la dialyse peritoneale chez l'enfant. La pharmacocinetique de la gentamycine a ete etudiee a deux reprises en utilisant les voies d'adminstration intra-veineuse et intraperitoneale chez 5 enfants soumis a des dialyses peritoneales periodiques pour insuffisance renale chronique. La gentamycine a ete dosee dans le serum, l'urine et le liquide de dialyse et les resultats ont ete traites en utilisant les equations d'un modele a deux compartiments qui prend en compte les flux bi-directionnels de la drogue. Apres l'injection i.v. de 1 mg/kg de gentamycine le volume apparent de distribution est en moyenne de 23% (13 a 36) du poids corporel, (valeur similaire a la normale), la demie vie moyenne de 21 heures (9 a 37) alores qu'elle est de 2 heures normalement et la clearance peritoneale est en moyenne de 4,0 ml/min/m 2 (1,2 a 7,0). Au cours de l'administration peritoneale de gentamycine (15 mg/l de liquide de dialyse, 0,7 l/m 2 a chaque cycle, 9 a 12 cycles) la concentration serique augmente vers un plateau, calcule par extrapolation, de 42% (25 a 68) de la concentration dans le liquide de dialyse. La clearance renale moyenne de la gentamycine etait de 1,6 ml/min/m 2 alors que la clearance totale allait de 2,3 a 8,0 ml/min/m 2 , surtout liee a un degre variable de dialysance. Les clearances peritoneales et les demies vies de la gentamycine etaient semblables chez le meme malade apres l'administration intra-veineuse ou intra-peritoneale. La variabilite importante de la pharmacocinetique de la gentamycine chez les malades adolescents atteints d'insuffisance renale necessite des ajustements de posologie fondes sur la determination des concentrations seriques.