CLINICAL PHARMACOLOGY
Pharmacokinetics
ORACEA capsules are not bioequivalent to other doxycycline products. The pharmacokinetics of doxycycline following oral administration of ORACEA was investigated in 2 volunteer studies involving 61 adults. Pharmacokinetic parameters for ORACEA following single oral doses and at steady-state in healthy subjects are presented in Table 1.
Table 1. Pharmacokinetic Parameters [Mean (± SD)] for ORACEA | | N | Cmax
(ng/mL) | Tmax Median
(hr) | AUC0-∞
(ng∙hr/mL) | t1/2
(hr) |
|---|
Single Dose
40 mg capsules | 30 | 510 ±
220.7 | 3.00
(1.0-4.1) | 9227 ±
3212.8 | 21.2 ±
7.6 |
|---|
Steady-StateDay 7
40 mg capsules | 31 | 600 ±
194.2 | 2.00
(1.0-4.0) | 7543 ±
2443.9 | 23.2 ±
6.2 |
|---|
Absorption
In a single-dose food-effect study involving administration of ORACEA to healthy volunteers, concomitant administration with a 1000 calorie, high-fat, high-protein meal that included dairy products, resulted in a decrease in the rate and extent of absorption (Cmax and AUC) by about 45% and 22%, respectively, compared to dosing under fasted conditions. This decrease in systemic exposure can be clinically significant, and therefore if ORACEA is taken close to meal times, it is recommended that it be taken at least one hour prior to or two hours after meals.
Distribution
Doxycycline is greater than 90% bound to plasma proteins.
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 reported that between 29% and 55.4% of an administered dose can be accounted for in the urine by 72 hours. Terminal half-life averaged 21.2 hours in subjects receiving a single dose of ORACEA.
Special Populations
Geriatric
Doxycycline pharmacokinetics have not been evaluated in geriatric patients.
Pediatric
Doxycycline pharmacokinetics have not been evaluated in pediatric patients (see WARNINGS section).
Gender
The pharmacokinetics of ORACEA were compared in 16 male and 14 female subjects under fed and fasted conditions. While female subjects had a higher Cmax and AUC than male subjects, these differences were thought to be due to differences in body weight/lean body mass.
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 serum half-life of doxycycline.
Hepatic Insufficiency
Doxycycline pharmacokinetics have not been evaluated in patients with hepatic insufficiency.
Gastric Insufficiency
In a study in healthy volunteers (N=24) the bioavailability of doxycycline is reported to be reduced at high pH. This reduced bioavailability may be clinically significant in patients with gastrectomy, gastric bypass surgery or who are otherwise deemed achlorhydric.
Drug Interactions
(see PRECAUTIONS section)
MICROBIOLOGY
Doxycycline is a member of the tetracycline class of antibacterial drugs. The plasma concentrations of doxycycline achieved with ORACEA during administration (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION) are less than the concentration required to treat bacterial diseases. In vivo microbiological studies utilizing a similar drug exposure for up to 18 months demonstrated no detectable long-term effects on bacterial flora of the oral cavity, skin, intestinal tract, and vagina.
ORACEA should not be used for treating bacterial infections, providing antibacterial prophylaxis, or reducing the numbers or eliminating microorganisms associated with any bacterial disease.
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