Doxyderm

Pharmacotherapeutic group: Tetracyclines, ATC code: J01 AA02.

Doxyderm is primarily bacteriostatic and is believed to exert its antimicrobial effect by the inhibition of protein synthesis. Doxyderm is active against a wide range of Gram-positive and Gram-negative bacteria and certain other micro-organisms.

Pharmacotherapeutic group: Tetracyclines, ATC code: J01 AA02

Doxyderm is primarily bacteriostatic and is believed to exert its antimicrobial effect by the inhibition of protein synthesis. Doxyderm is active against a wide range of Gram-positive and Gram-negative bacteria and certain other micro-organisms.

Pharmacotherapeutic group: Tetracyclines

ATC code: J01A A02

The active ingredient of Doxyderm, doxycycline, is synthetically derived from oxytetracycline, with a molecular formula of C₂₂H₂₄N₂O₈-HCl-½ C₂H₅OH-½ H₂O.

Doxyderm is an inhibitor of collagenase activity. Studies have shown that at the proposed 20 mg b.i.d. dose level, Doxyderm reduces the elevated collagenase activity in the gingival crevicular fluid of patients with chronic adult periodontitis, whilst not demonstrating any clinical evidence of anti-microbial activity.

Susceptibility

The dosage achieved with this product during administration is well below the concentration required to inhibit microorganisms commonly associated with adult periodontitis. Clinical studies with this product demonstrated no effect on total anaerobic and facultative bacteria in plaque samples from patients administered this dose regimen for 9 to 18 months. This product SHOULD NOT be used for reducing the numbers of, or eliminating, those microorganisms associated with periodontitis.

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. 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.

Absorption

Tetracyclines are readily absorbed and are bound to proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and faeces at high concentration and in a biologically active form. Doxyderm is virtually completely absorbed after oral administration. Studies reported to date indicate that the absorption of Doxyderm unlike certain other tetracyclines, is not notably influenced by the ingestion of food or milk.

Following a 200mg dose, normal adult volunteers averaged peak serum levels of 2.6 micrograms/ml at 2hours decreasing to 1.45micrograms/ml at 24 hours. Doxyderm has a high degree of lipid solubility and a low affinity for calcium. It is highly stable in normal human serum. Doxyderm will not degrade into an epianhydro form.

Absorption

Following administration of a single dose of Doxyderm MPC under fasting conditions, the AUCinf and Cmax were 26.7 mcg-h/mL and 1.6 mcg/mL, respectively. The Tmax was 2.8 hours. In a single-dose study to evaluate the relative bioavailability in healthy adult subjects under fasted conditions, Doxyderm MPC 120 mg Tablets were found to be bioequivalent to Doxyderm 100 mg Tablets. When a single dose of Doxyderm MPC 120 mg Tablet was administered with a standardized high-fat high-calorie meal, (937kcal consisting of approximately 55% fat, 30% carbohydrate and 15% protein), the Cmax was approximately 30% lower, but there was no significant difference in the AUCinf compared to administration under fasting conditions.

Excretion

Tetracyclines are concentrated in bile by the liver and excreted in the urine and feces at high concentrations and in a biologically active form. Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with a creatinine clearance of about 75 mL/min. This percentage may fall as low as 1-5%/72 hours in individuals with a creatinine clearance below 10 mL/min.

Studies have shown no significant difference in the serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function. Hemodialysis does not alter the serum half-life.

Absorption:

Doxycycline is almost completely absorbed after oral administration. Following ingestion of 20 mg doxycycline twice daily, mean maximum plasma concentrations were 0.79 µg/ml. Peak levels were generally achieved 2 hours after administration. Food intake reduced the extent of absorption by 10% and decreased and delayed the peak plasma levels.

Distribution:

Doxycycline is greater than 90% bound to plasma proteins and has an apparent volume of distribution of 50L.

Metabolism:

Major metabolic pathways of doxycycline have not been identified, however, enzyme inducers decrease the half-life of doxycycline.

Elimination:

Doxycycline is excreted in the urine and faeces as unchanged drug. Between 40% and 60% of an administered dose can be accounted for in the urine by 92 hours, and approximately 30% in the faeces. The terminal half-life after a single 20 mg doxycycline dose averaged 18h.

Special populations:

The half-life is not significantly altered in patients with severely impaired renal function. Doxycycline is not eliminated to any great extent during haemodialysis.

Not applicable.

None known

Not applicable.