Clinical pharmacokinetics of teicoplanin. 1990

M Rowland
Department of Pharmacy, University of Manchester, England.

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.

UI MeSH Term Description Entries
D007674 Kidney Diseases Pathological processes of the KIDNEY or its component tissues. Disease, Kidney,Diseases, Kidney,Kidney Disease
D010531 Peritoneal Dialysis, Continuous Ambulatory Portable peritoneal dialysis using the continuous (24 hours a day, 7 days a week) presence of peritoneal dialysis solution in the peritoneal cavity except for periods of drainage and instillation of fresh solution. CAPD,Continuous Ambulatory Peritoneal Dialysis
D006020 Glycopeptides Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight. Glycopeptide
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000042 Absorption The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D017334 Teicoplanin Lipoglycopeptide antibiotic from Actinoplanes teichomyceticus active against gram-positive bacteria. It consists of five major components each with a different fatty acid moiety. Teichomycin,Targocid,Teichomycin A2

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