Clinical Pharmacokinetics of Vancomycin

Abstract

Vancomycin utilisation has increased dramatically in the last 10 years due to the increasing clinical significance of infections with methicillin-resistant staphylococci. Recent studies have focused on characterising the disposition of vancomycin in patients and assessing the relationship between serum concentrations and therapeutic as well as adverse effects. Although vancomycin is not appreciably absorbed from the intact gastrointestinal tract, several recent case reports have documented the attainment of therapeutic and potentially toxic vancomycin serum concentrations following oral administration to patients with pseudomembranous colitis. The disposition of parenterally administered vancomycin has been best characterised by a triexponential model. The half-life of the initial phase (t1/2 pi) is approximately 7 minutes, that of the second phase (t1/2 alpha) is approximately 0.5 to 1 hour, while the terminal elimination half-life (t1/2 beta) ranges from 3 to 9 hours in subjects with normal renal function. The volume of the central compartment (Vc) in adults is approximately 0.15 L/kg while the steady-state volume of distribution (Vdss) ranges from 0.39 to 0.97 L/kg. More than 80% of a vancomycin dose is excreted unchanged in the urine within 24 hours after administration, and the concentration of vancomycin in liver tissue and bile has been reported to be at or below detection limits. Vancomycin renal clearance approximates 0.5 to 0.8 of simultaneously determined creatinine or 125I-iothalamate clearances, suggesting that the primary route of renal excretion is glomerular filtration. Recently, non-renal factors such as hepatic conjugation have been proposed as an important route of vancomycin elimination. However, these data are difficult to reconcile with other studies showing minimal non-renal clearance of vancomycin in subjects with end-stage renal disease. As yet, the disposition of vancomycin in patients with hepatic disease has not been adequately defined. Only limited data are available regarding the concentrations of vancomycin in biological fluids other than plasma. The penetration of vancomycin into cerebrospinal fluid (CSF) in patients with and without meningitis has been quite variable. Although early studies suggested that adequate CSF concentrations may not be achieved in subjects with uninflamed meninges, more recent investigations have reported contradictory results. Therapeutic concentrations of vancomycin, i.e. greater than 2.5 mg/L, have, however, been reported in ascitic, pericardial, pleural and synovial fluids. Tissue concentrations of vancomycin have exceeded simultaneous serum concentrations in heart, kidney, liver and lung sp

Monitoring the treatment of sepsis with vancomycin in term newborn infants

“…Other authors report the relationship between SBT levels of 1/8 at the serum trough and successful healing in 95% of the pediatric patients (with ages varying from 3 days to 12 years) 27 . In our results, there was one case in which it was necessary to maintain the serum concentration of vancomycin above 12 mg/mL to obtain a trough SBT of 1/8.…”

“…A single compartmental model has also been used in recent studies of the pharmacokinetics of vancomycin in premature infants. Although there may be shortcomings in the use of the single compartmental model, it is believed that these are not clinically significant [27][28][29][30][31][32] .…”

“…When the serum concentration of vancomycin is collected at the peak, the objective is to diagnose the potential risk for ototoxicity, although there is limited information in the literature regarding this possible toxic effect related to vancomycin in newborns 27 .…”

“…The nephrotoxicity due to vancomycin is associated to trough serum concentrations above 30 mg/mL 27 .…”

Therapeutic drug monitoring of vancomycin in a patient with Duchenne muscular dystrophy (DMD): A case report

“…Since vancomycin is known to be eliminated primarily via renal excretion, estimating the renal function of a patient as well as the serum vancomycin concentration is considered essential. [2] Creatinine is produced constantly by the skeletal muscles, and is mainly eliminated via glomerular filtration and not reabsorbed or secreted. Therefore, the serum creatinine level (SCr) is widely used as an indicator of glomerular filtration rate (GFR), which is an index of renal function in clinical practice.…”