Chemical formula: C₈₈H₉₇Cl₂N₉O₃₃ Molecular mass: 1,879.7 g/mol
Teicoplanin inhibits the growth of susceptible organisms by interfering with cell-wall biosynthesis at a site different from that affected by beta-lactams. Peptidoglycan synthesis is blocked by specific binding to D-alanyl-D-alanine residues.
Resistance to teicoplanin can be based on the following mechanisms:
Cross-resistance between teicoplanin and the glycoprotein vancomycin may occur. A number of vancomycin-resistant enterococci are sensitive to teicoplanin (Van-B phenotype).
Teicoplanin antimicrobial activity depends essentially on the duration of time during which the substance level is higher than the minimum inhibitory concentration (MIC) of the pathogen.
Teicoplanin is administered by parenteral route (intravenously or intramuscularly). After intramuscular administration, the bioavailability of teicoplanin (as compared to intravenous administration) is almost complete (90%). After six daily intramuscular administrations of 200 mg the mean (SD) maximum teicoplanin concentration (Cmax) amounts to 12.1 (0.9) mg/L and occurs at 2 hours after administration.
After a loading dose of 6 mg/kg administered intravenously every 12 hours for 3 to 5 administrations, Cmax values range from 60 to 70 mg/L and Ctrough are usually above 10 mg/L. After an intravenous loading dose of 12 mg/kg administered every 12 hours for 3 administrations, mean values of Cmax and Ctrough are estimated to be around 100 mg/L and 20 mg/L, respectively.
After a maintenance dose of 6 mg/kg administered once daily Cmax and Ctrough values are approximately 70 mg/L and 15 mg/L, respectively. After a maintenance dose of 12 mg/kg once daily Ctrough values range from 18 to 30 mg/L.
When administered by oral route teicoplanin is not absorbed from the gastrointestinal tract. When administered by oral route at 250 or 500 mg single dose to healthy subjects, teicoplanin is not detected in serum or urine but only recovered in feces (about 45% of the administered dose) as unchanged medicinal product.
The binding to human serum proteins ranges from 87.6 to 90.8% without any variation in function of the teicoplanin concentrations. Teicoplanin is mainly bound to human serum albumin. Teicoplanin is not distributed in red cells.
The volume of distribution at steady-state (Vss) varies from 0.7 to 1.4 L/kg. The highest values of Vss are observed in the recent studies where the sampling period was superior to 8 days.
Teicoplanin distributed mainly in lung, myocardium and bone tissues with tissue/serum ratios superior to 1. In blister fluids, synovial fluid and peritoneal fluid the tissue/serum ratios ranged from 0.5 to 1. Elimination of teicoplanin from peritoneal fluid occurs at the same rate as from serum. In pleural fluid and subcutaneous fat tissue the tissue/serum ratios are comprised between 0.2 and 0.5. Teicoplanin does not readily penetrate into the cerebrospinal fluid (CSF).
Unchanged form of teicoplanin is the main compound identified in plasma and urine, indicating minimal metabolism. Two metabolites are formed probably by hydroxylation and represents 2 to 3% of the administered dose.
Unchanged teicoplanin is mainly excreted by urinary route (80% within 16 days) while 2.7% of the administered dose is recovered in feces (via bile excretion) within 8 days following administration.
Elimination half-life of teicoplanin varies from 100 to 170 hours in the most recent studies where blood sampling duration is about 8 to 35 days.
Teicoplanin has a low total clearance in the range of 10 to 14 mL/h/kg and a renal clearance in the range of 8 to 12 mL/h/kg indicating that teicoplanin is mainly excreted by renal mechanisms.
Teicoplanin exhibited linear pharmacokinetics at dose range of 2 to 25 mg/kg.
As teicoplanin is eliminated by renal route, teicoplanin elimination decreases according to the degree of renal impairment. The total and renal clearances of teicoplanin depends on the creatinine clearance.
In the elderly population the teicoplanin pharmacokinetics is not modified unless in case of renal impairment.
A higher total clearance (15.8 mL/h/kg for neonates, 14.8 mL/h/kg for a mean age 8 years) and a shorter elimination half-life (40 hours neonates; 58 hours for 8 years) are observed compared to adult patients.
Following repeated parenteral administration to the rat and dog, effects on the kidney were observed and were shown to be dose-dependent and reversible. Studies to investigate the potential to cause ototoxicity in the guinea-pig indicate that a mild impairment of cochlear and vestibular function is possible, in the absence of morphological damage.
Subcutaneous administration of teicoplanin at up to 40 mg/kg/day did not affect male and female fertility in the rat. In embryofetal development studies, no malformations were observed following subcutaneous administration of up to 200 mg/kg/day in the rat and intramuscular administration up to 15 mg/kg/day in the rabbit. However, in the rat, there was an increased incidence of stillbirths at doses of 100 mg/kg/day and above and neonatal mortality at 200 mg/kg/day. This effect was not reported at 50 mg/kg/day. A peri and postnatal study in rats showed no effects on the fertility of the F1 generation or on the survival and development of the F2 generation following subcutaneous administration of up to 40 mg/kg/day.
Teicoplanin did not show any potential to cause antigenicity (in mice, guinea-pigs or rabbits), genotoxicity or local irritancy.
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