Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1. Pharmacodynamic Properties
Pharmacotherapeutic group: Tetracyclines, ATC code: J01AA02.
Doxycycline is primarily bacteriostatic and is believed to exert its antimicrobial effect by the inhibition of protein synthesis. Doxycycline is active against a wide range of Gram-positive and Gram-negative bacteria and certain other micro-organisms.
Doxycycline has a high degree of lipid solubility and a low affinity for calcium. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form.

Pharmacokinetic Properties

5.2. Pharmacokinetic Properties

Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and faeces at high concentrations and in a biologically active form. Doxycycline is virtually completely absorbed after oral administration. Studies reported to date indicate that the absorption of doxycycline, unlike certain other tetracyclines, is not notably influenced by the ingestion of food or milk.
Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 micrograms/ml of doxycycline at 2 hours decreasing to 1.45 micrograms/ml at 24 hours. Studies have shown no significant differences in serum half-life of Doxycycline (range 18 to 22 hours) in individuals with normal or severely impaired renal function.
Haemodialysis does not alter the serum half-life of Doxycycline.
Children and Adolescents (2 to 18 years of age)
Population pharmacokinetic analysis of sparse concentration-time data of doxycycline following standard of care intravenous (IV) and oral dosing in 44 paediatric patients (2-18 years of age) showed that allometrically-scaled clearance (CL) of doxycycline in paediatric patients ≥2 to ≤8 years of age (median [range] 3.58 [2.27-10.82] L/h/70 kg, N=11) did not differ significantly from paediatric patients >8 to 18 years of age (3.27 [1.11-8.12] L/h/70 kg, N=33). For paediatric patients weighing ≤45 kg, body weight normalized doxycycline CL in those ≥2 to ≤8 years of age (median [range] 0.071 [0.041-0.202] L/kg/h, N=10) did not differ significantly from those >8 to 18 years of age (0.081 [0.035-0.126] L/kg/h, N=8). In paediatric patients weighing >45 kg, no clinically significant differences in body weight normalized doxycycline CL were observed between those ≥2 to ≤8 years (0.050 L/kg/h, N=1) and those >8 to 18 years of age (0.044 [0.014- 0.121] L/kg/h, N=25). No clinically significant difference in CL between oral and IV dosing was observed in the small cohort of paediatric patients who received the oral (N=19) or IV (N=21) formulation alone.