RESUMEN
Clindamycin is widely used in antimicrobial prophylaxis to prevent surgical site infections. Adequate subcutaneous free tissue concentrations should reach therapeutic levels, which have to be maintained throughout the surgical procedure for antibiotic prophylaxis to be efficient. A method was developed and validated using high performance liquid chromatography coupled to a mass spectrometry to determine clindamycin concentrations in two biological matrices: plasma, for drug monitoring, and subcutaneous microdialysate, to determine free concentrations at the incision site. Gradient separation of clindamycin was carried out using a reverse phase C18 column eluted with a mixture of mobile phases (1% formic acid in water and 1% formic acid in acetonitrile). The monitored transitions were m/z 425.3â¯>â¯377.3 for clindamycin, and m/z 407â¯>â¯359 for lincomycin, used as the internal standard for plasma samples. Linearity was reached in the 0.5-100⯵g/mL range for plasma and 25-1000â¯ng/mL for microdialysate samples. The method was selective, precise, and accurate, and was successfully employed in a preliminary pharmacokinetics study to investigate plasma and subcutaneous clindamycin penetration, determined by microdialysis, after intravenous administration of a 50â¯mg/kg dose to Wistar rats.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Clindamicina/sangre , Clindamicina/farmacocinética , Plasma/química , Espectrometría de Masas en Tándem/métodos , Administración Intravenosa/métodos , Animales , Antibacterianos/sangre , Antibacterianos/farmacocinética , Masculino , Microdiálisis/métodos , Ratas , Ratas Wistar , Reproducibilidad de los ResultadosRESUMEN
The pharmacokinetics of intravenously administered clindamycin phosphate was studied in 40 children less than 1 year of age. Mean peak serum concentrations were 10.92 micrograms/ml in premature infants less than 4 weeks of age, 10.45 micrograms/ml in term infants greater than 4 weeks, and 12.69 micrograms/ml in term infants less than 4 weeks of age. Mean trough concentrations were 5.52, 2.8, and 3.03 micrograms/ml, respectively, in the same groups. Serum half-life was significantly longer (8.68 vs 3.60 hours) in premature compared with term infants less than 4 weeks of age. Both premature and term infants less than 4 weeks had significantly decreased clearance when compared with infants greater than 4 weeks (0.294 and 0.678, respectively, vs 1.58 L/hr). Clearance was significantly greater (1.919 vs 0.310 L/hr) and serum half-life less (1.75 vs 7.57 hours) in infants with body weight greater than 3.5 kg. On the basis of these data it is recommended that in infants greater than 4 weeks or greater than 3.5 kg, intravenous clindamycin dosage be 20 mg/kg/day in four divided doses. In premature neonates less than 4 weeks, the dose should be reduced to 15 mg/kg/day in three divided doses. Term infants greater than 1 week of age may also receive 20 mg/kg/day in four doses.