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After oral administration, doxycycline hyclate is rapidly and nearly completely absorbed from the gastrointestinal tract. Doxycycline is eliminated with a half-life of approximately 18 hours by renal and fecal excretion of unchanged drug.
Mechanism of Action: Doxycycline has been shown to inhibit collagenase activity in vitro.1 Additional studies have shown that doxycycline reduces the elevated collagenase activity in the gingival crevicular fluid of patients with adult periodontitis.2,3 The clinical significance of these findings is not known.
Microbiology: Doxycycline is a member of the tetracycline class of antibiotics. The dosage of doxycycline 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.
The pharmacokinetics of doxycycline following oral administration of Periostat® (doxycycline hyclate) were investigated in 4 volunteer studies involving 107 adults. Additionally, doxycycline pharmacokinetics have been characterized in numerous scientific publications.4 Pharmacokinetic parameters for Periostat® (doxycycline hyclate) following single oral doses and at steady-state in healthy subjects are presented as follows:
Pharmacokinetic Parameters for Periostat® (doxycycline hyclate)
|Single dose 20 mg (tablet)||20||362 ± 101||1.4
|3.85 ± 1.3||18.1 ± 4.85|
|Steady-State 20 mg 20 mg BID***||30||790 ± 285||2
(0.98 - 12.0)
|3.76 ± 1.06||Not Determined|
| * Mean ± SD
** Mean and range
*** Steady-State data were obtained from normal volunteers administered a bioequivalent formulation.
Absorption: Doxycycline is well absorbed after oral administration. In a single-dose study, concomitant administration of Periostat® (doxycycline hyclate) with a 1000 calorie, high-fat, high-protein meal which included dairy products, in healthy volunteers, resulted in a decrease in the rate and extent of absorption and delay in the time to maximum concentrations.
Distribution: Doxycycline is greater than 90% bound to plasma proteins. Its apparent volume of distribution is variously reported as between 52.6 and 134 L.4,6
Metabolism: Major metabolites of doxycycline have not been identified. However, enzyme inducers such as barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.
Excretion: Doxycycline is excreted in the urine and feces as unchanged drug. It is variously reported that between 29% and 55.4% of an administered dose can be accounted for in the urine by 72 hours.5,6 Half-life averaged 18 hours in subjects receiving a single 20 mg doxycycline dose.
Geriatric: Doxycycline pharmacokinetics have not been evaluated in geriatric patients.
Pediatric: Doxycycline pharmacokinetics have not been evaluated in pediatric patients (See WARNINGS section).
Gender: Doxycycline pharmacokinetics were compared in 9 men and 11 women under fed and fasted conditions. While female subjects had a higher rate (Cmax) and extent of absorption (AUC), these differences are thought to be due to differences in body weight/lean body mass. Differences in other pharmacokinetic parameters were not significant.
Race: Differences in doxycycline pharmacokinetics among racial groups have not been evaluated.
Renal Insufficiency: Studies have shown no significant difference in serum half-life of doxycycline in patients with normal and severely impaired renal function. Hemodialysis does not alter the half-life of doxycycline.
Hepatic Insufficiency: Doxycycline pharmacokinetics have not been evaluated in patients with hepatic insufficiency.
Drug Interactions: (See PRECAUTIONS section)
In a randomized, multi-centered, double-blind, 9-month Phase 3 study involving 190 adult patients with periodontal disease [at least two probing sites per quadrant of between 5 and 9 mm pocket depth (PD) and attachment level (ALv)], the effects of oral administration of 20 mg twice a day of doxycycline hyclate (using a bioequivalent capsule formulation) plus scaling and root planing (SRP) were compared to placebo control plus SRP. Both treatment groups were administered a course of scaling and root planing in 2 quadrants at Baseline. Measurements of ALv, PD and bleeding-on-probing (BOP) were obtained at Baseline, 3, 6, and 9 months from each site about each tooth in the two quadrants that received SRP using the UNC-15 manual probe. Each tooth site was categorized into one of three strata based on Baseline PD: 0-3 mm (no disease), 4-6 mm (mild/moderate disease), ≥ 7 mm (severe disease). For each stratum and treatment group, the following were calculated at month 3, 6, and 9: mean change in ALv from baseline, mean change in PD from baseline, mean percentage of tooth sites per patient exhibiting attachment loss of ≥ 2 mm from baseline, and percentage of tooth sites with bleeding on probing. The results are summarized in the following table.
Clinical Results at Nine Months of Doxycycline Hyclate Capsules,
20 mg, as an Adjunct to SRP (Bioequivalent to Doxycycline Hyclate Tablets, 20
|Parameter||Baseline Pocket Depth|
|0-3 mm||4-6 mm||≥ 7 mm|
|Number of Patients (Periostat®20mg BID)||90||90||79|
|Number of Patients (Placebo)||93||93||78|
|Mean Gain (SDƒƒ) in ALv√|
|Periostat® 20 mg BID||0.25 (0.29) mm||1.03 (0.47) mm*||1.55 (1.16) mm*|
|Placebo||0.20 (0.29) mm||0.86 (0.48) mm||1.17 (1.15) mm|
|Mean Decrease (SDƒƒ) in PD√√|
|Periostat® 20 mg BID||0.16 (0.19) mm**||0.95 (0.47) mm**||1.68 (1.07) mm**|
|Placebo||0.05 (0.19) mm**||0.69 (0.48) mm**||1.20 (1.06) mm**|
|% of Sites (SDƒƒ) with loss of ALv√ ≥ 2 mm|
|Periostat® 20 mg BID||1.9 (4.2)%||1.3 (4.5)%||0.3 (9.4)%*|
|Placebo||2.2 (4.1)%||2.4 (4.4)%||3.6 (9.4)%*|
|% of Sites (SDƒƒ) with BOPƒ|
|Periostat® 20 mg BID||39 (19)%**||64 (18)%*||75 (29)%|
|Placebo||46 (19)%**||70 (18)%||80 (29)%|
| * p < 0.050 vs. the placebo control group.
** p < 0.010 vs. the placebo control group.
√ Alv = Clinical Attachment Level
√ √ PD = Pocket Depth
ƒBOP = Bleeding on Probing
ƒƒSD = Standard Deviation
1. Golub L.M., Sorsa T., Lee H-M, Ciancio S., Sorbi D., Ramamurthy N.S., Gruber B., Salo T., Konttinen Y.T.: Doxycycline Inhibits Neutrophil (PMN)-type Matrix Metalloproteinases in Human Adult Periodontitis Gingiva. J. Clin. Periodontol 1995; 22: 100-109.
2. Golub L.M., Ciancio S., Ramamurthy N.S., Leung M., McNamara T.F.: Low-dose Doxycycline Therapy: Effect on Gingival and Crevicular Fluid Collagenase Activity in Humans. J. Periodont Res 1990; 25: 321-330.
3. Golub L.M., Lee H.M., Greenwald R.A., Ryan M.E., Salo T., Giannobile W.V.: A Matrix Metalloproteinase Inhibitor Reduces Bone-type Collagen Degradation Fragments and Specific Collegenases in Gingival Crevicular Fluid During Adult Periodontitis. Inflammation Research 1997; 46: 310-319.
4. Saivain S., Houin G.: Clinical Pharmacokinetics of Doxycycline and Minocycline. Clin. Pharmacokinetics 1988; 15; 355-366.
5. Schach von Wittenau M., Twomey T.: The Disposition of Doxycycline by Man and Dog. Chemotherapy 1971; 16: 217-228.
6. Campistron G., Coulais Y., Caillard C., Mosser J., Pontagnier H., Houin G.: Pharmacokinetics and Bioavailability of Doxycycline in Humans. Arzneimittel Forschung 1986; 36: 1705-1707.
Last reviewed on RxList: 10/29/2008
This monograph has been modified to include the generic and brand name in many instances.
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