Pharmacokinetics of Vancomycin Hydrochloride (VCM) in Dialysis Patients.

Abstract

Vancomycin hydrochloride (VCM) is widely used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. However, this drug can cause severe adverse reactions, such as nephrotoxicity and ototoxicity. As a result, monitoring the blood concentration of VCM is recommended. As VCM is excreted from the kidney without undergoing any metabolic changes, it is necessary to determine the loading dose of VCM and to monitor its blood concentration in patients with renal dysfunction. In patients with renal dysfunction, the loading dose of this drug can be determined using a nomogram. Although there have been various reports on the pharmacokinetics of VCM in both continuous ambulatory peritoneal dialysis (CAPD) patients and hemodialysis (HD) patients, no conclusive findings have yet been reported. The present study therefore investigated the pharmacokinetics of VCM in six patients with MRSA-induced CAPD peritonitis and five HD patients with an MRSA infection. Of the six patients with CAPD peritonitis, VCM was administered intravenously to one patient, intraperitoneally via the CAPD bag to two patients, and by a combination of these two methods to three patients. In terms of the VCM doses, 20 mg/kg were administered intravenously to the CAPD and HD patients, and 30 mg/kg were administered intraperitoneally via the CAPD bag. The blood concentration, pharmacokinetic parameters, inflammation findings, clinical effects and clinical laboratory tests were analyzed. When VCM was administered intravenously to CAPD patients, its half-life varied greatly from one treatment to the next and from one patient to the next, with the administration time ranging from 37.7 to 341 hours. Nonetheless, the tendency was as follows : the more improved the peritonitis, the longer the half-life of the drugs. These findings suggest that it will be necessary to determine the dose of administration and the interval each time VCM is administered intravenously, and to monitor its pharmacokinetics and inflammation parameters. When VCM was administered intraperitoneally via the CAPD bag, the transfer of the drug to blood was confirmed, and its pharmacokinetic parameters were also comparable among the patients. These findings suggest that the pharmacokinetics of this drug are therefore more stable when it is administered via a CAPD bag. Furthermore, a regression analysis showed an extremely high correlation between the VCM concentration in the blood and the drainage of CAPD during the elimination phase (Y = 1.046X +4.978, r = 0.95, p< 0.01). Moreover, the pharmacokinetics of VCM differed greatly between intraperitoneal and intravenous administrations in CAPD patients. In HD patients, the half-life of VCM ranged widely from 12.3 to 86.1 hours, and its distribution volume ranged from 0.55 to 1.96 L/kg. The removal rate of VCM with B 3 series dialysis utilizing a polymethyl methacrylate (PMMA) dialysis membrane ranged from 17.3 to 26.2%.When VCM was administered intravenously to HD and CAPD patients, its pharmacokinetics varied greatly from one treatment to the next and from one patients to the next. It is therefore necessary to monitor the blood concentration of VCM each time this drug is administered intravenously. On the other hand, when VCM was administered intraperitoneally via the CAPD bag, its pharmacokinetics did not differ markedly from one patient to the next, thus suggesting that the blood concentration of VCM could thus be accurately estimated by measuring its concentration in the drainage of the CAPD.