PHARMACOKINETICS OF CEFTRIAXONE IN PATIENTS WITH TYPHOID-FEVER

Ceftriaxone in short courses has emerged as an effective alternative t o chloramphenicol for the treatment of typhoid fever. To study the pha rmacokinetics of ceftriaxone in acute typhoid fever, 10 febrile Nepale se adolescents and young adults with blood culture-positive illness we re treated with 3 g of ceftriaxone (intravenous infusion for 30 min) d aily for 3 days. On the Ist and 3rd day of treatment, blood and urine samples were collected at defined intervals for measurements of drug c oncentrations. Kinetic parameters including concentrations at the end of infusion (C-max) and 24 h after the end of infusion (C-min), elimin ation half-life (t(1/2)), area under the plasma concentration-time cur ve (AUC), total plasma clearance, renal clearance, percentage excreted in urine, and volume of distribution were estimated. On day 1, mean v alues were as follows: C-max, 291 mu g/ml; C-min, 21.7 mu g/ml; plasma t(1/2), 5.2 h; AUC, 1,428 mu g.h/ml; total plasma clearance, 37 ml/mi n; renal clearance, 19 ml/min; percentage excreted in urine, 49.7%; an d volume of distribution, 16.1 liters. Mean values on day 3 were not s ignificantly different from those on day 1. Compared with published va lues for healthy volunteers who received the same dose, our mean t(1/2 )s and AUCs were lower and our mean total plasma clearances, renal cle arances, and volumes of distribution were higher. The good clinical re sponses of these patients to therapy and the adequate C,,,s support th e use of ceftriaxone once daily for the treatment of typhoid fever.