Clinical pharmacokinetics of teicoplanin

Abstract

Teicoplanin is a recently introduced glycopeptide antibiotic for the treatment of a variety of aerobic and anaerobic Gram-positive infections. It is a mixture of 5 closely related components, of similar polarity and biological activity, and 1 or more polar hydrolysis products. Teicoplanin is rapidly and extensively absorbed from muscle and the peritoneal cavity but very poorly absorbed from the gastrointestinal tract. Following intravenous administration, the disposition kinetics are best described by a tri-exponential equation, and the majority of drug is excreted unchanged, by glomerular filtration. In patients with normal renal function, the half-lives of the first, second and terminal phases are 35 minutes, 10 hours and 87 hours, respectively. The initial volume of distribution is 0.089 L/kg, the volume of distribution at steady-state is 0.86 L/kg, clearance is 0.0114 L/h/kg and renal clearance is 0.0083 L/h/kg. Teicoplanin is highly bound in plasma to albumin (fraction unbound = 0.1) and in tissues. The pharmacokinetics are linear over a wide dose range (2 to 26 mg/kg). The minor differences in the pharmacokinetics of the components of teicoplanin can be accounted for by differences in lipophilicity. The events following multiple dosing are predicted from single dose data; renal clearance decreases in patients with renal insufficiency in a predictable manner. Negligible drug is lost during haemodialysis. As expected, clearance per kilogram is higher in children than in adults, and lower in the elderly, associated with a decrease in glomerular filtration rate with advancing years. Tissue distribution data are limited. Concentrations, relative to those in plasma, are high in lung and bone tissue and low in fat. Animal data show high concentrations in most tissues, and particularly high in liver and kidneys. Teicoplanin penetrates slowly and poorly into cerebrospinal fluid, but relatively rapidly and effectively in synovial and pleural fluids and in soft tissue. The manufacturer's recommended intravenous or intramuscular dosage regimens rapidly achieve and maintain adequate plasma concentrations of teicoplanin; the dosing interval is usually 1 day. The maintenance dosing rate, but not the loading dose (if needed), must be reduced in patients with poor renal function and in the elderly. For those patients on continuous ambulatory peritoneal dialysis, the peritoneal cavity offers a convenient alternative route of drug administration.