Although it was previously suggested that doxycycline is partially metabolized in the liver, recent studies indicate that the drug is not metabolized but is partially deactivated in the intestine by chelate formation.
Doxycycline has been associated with rare instances of hepatic injury, generally arising within 1 to 2 weeks of starting therapy, sometimes with a history of previous administration of the agent without injury. The pattern of injury ranges from hepatocellular to cholestatic and is probably most commonly mixed. The onset is often abrupt and can be accompanied by signs of hypersensitivity, such as fever, rash and eosinophilia (DRESS syndrome). Recovery is usually rapid and usually complete within 4 to 6 weeks. However, instances of severe and prolonged cholestatic liver injury have been reported with oral doxycycline. The autoimmune-like hepatitis that has been described with minocycline has not been linked to doxycycline, despite similarities in chemical structure and similar indications and uses, perhaps because it is used less frequency in a low dose, long term regimen. High dose intravenous doxycycline can cause acute fatty liver typical of that caused by intravenous tetracycline, particularly in susceptible patients such as pregnant women. This type of injury is, however, quite rare. Nevertheless, for these reasons, the duration and dose of parenteral doxycycline therapy should be minimized.
Minocycline therapy is associated with two forms of clinically apparent liver injury, an acute hepatitis-like syndrome that arises within 1 to 3 months of starting therapy and a chronic hepatitis-like syndrome typically with autoimmune features that occurs with long term therapy, sometimes after several years of use. There is some overlap between these two presentations of minocycline hepatotoxicity, both are associated with a hepatocellular pattern of serum enzyme elevations and both can be associated with autoantibodies and immunological features.
Minocycline has been linked to cases of an acute hepatitis with jaundice that typically arises within a few weeks or months of starting therapy. The enzyme elevations are typically hepatocellular and resemble acute viral hepatitis. Immunoallergic features are common and may be prominent with fever, rash and eosinophilia and some cases with facial edema, lymphoadenopathy and lymphocytosis that may resemble acute mononucleosis. The liver injury is usually self limited with complete resolution within 1 to 2 months of stopping. Some patients have autoimmune markers and these also improve upon stopping minocycline.
Minocycline has also been linked to cases of chronic hepatitis with or without jaundice that typically arise during long term therapy, sometimes after years of use. The most common presentation is with an autoimmune hepatitis-like syndrome that can be severe and even fatal, particularly if minocycline is not stopped promptly. Patients can present acutely with jaundice and fatigue or chronically with insidious onset of fatigue, joint aches and jaundice, usually after 6 months to many years of therapy. A hepatocellular pattern of enzyme elevations is typical with ALT levels ranging from 3- to 20-fold elevated depending upon the severity and duration of the injury. Autoantibodies are usually present, typically antinuclear antibody (ANA) at titers of >1:160. In some cases, ANA may initially be negative, arising later as the disease progresses or starts to improve. Immunoglobulins are also usually elevated and liver biopsy demonstrates changes typical of autoimmune hepatitis with active interface hepatitis, spotty eosinophilic necrosis and portal infiltrates rich in lymphocytes and plasma cells. Fibrosis is uncommon, but can occur, particularly if the disease is prolonged and minocycline continued in the face of hepatic injury. The condition will resolve spontaneously if minocycline is withdrawn, but corticosteroids are often used. In long term follow up after stopping minocycline, chronic injury is rare, if it occurs at all and generally all symptoms and laboratory test abnormalities resolve within 6 to 12 months of stopping, although patients may continue to have low titers of ANA.
Other immunologically mediated syndromes associated with minocycline use include a serum sickness like syndrome (generally within 3 to 12 weeks of starting), a lupus-like syndrome and hemolytic anemia (the latter two with chronic therapy). Liver injury can accompany these other autoimmune conditions, but is generally anicteric, mild and rapidly reversible. The pattern of serum enzyme elevations is typically hepatocellular and autoantibodies are common.
Likelihood score: A (well known cause of clinically apparent liver injury).
ORAL ADMIN OF FERROUS SULFATE (200-600 MG) INTERFERES WITH ABSORPTION OF ... /DOXYCYCLINE/ FROM GI TRACT & VICE VERSA, LEADING TO DECR SERUM LEVELS OF ANTIBIOTIC & IRON SALT, RESPECTIVELY. IF SIMULTANEOUS ADMIN IS NECESSARY, PATIENTS SHOULD RECEIVE ... /DOXYCYCLINE/ 3 HR AFTER OR 2 HR BEFORE IRON ADMIN.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
多西环素据报道会与氢氧化铝发生相互作用。
DOXYCYCLINE HAS BEEN REPORTED TO INTERACT WITH ALUMINUM HYDROXIDE.
The half-life of doxycycline may be decr by concurrent administration of carbamazepine (Tegretol), phenytoin (Dilantin), or barbiturates, which incr the hepatic metabolism of this antibiotic.
RELATIVE INSENSITIVITY OF DOXYCYCLINE PHARMACOKINETICS TO RENAL INSUFFICIENCY HAS ... BEEN DEMONSTRATED IN HUMANS & APPEARS TO BE ASSOC WITH INCR FECAL EXCRETION OWING TO DIFFUSION OF DRUG INTO LUMEN OF SMALL INTESTINE. ... RENAL CLEARANCE OF ACTIVE ANTIBIOTIC IS ... 20 ... ML/MIN FOR DOXYCYCLINE ... .
SERUM LEVELS OF DOXYCYCLINE ARE EQUIV WHETHER DRUG IS DOSED BY IV OR PER OS ROUTE. AFTER MULTIPLE DAILY IV DOSES OF 200 MG, SERUM LEVELS ... FLUCTUATED BETWEEN 5-6 & 1-2 UG/ML, WHICH IS ABOVE MIN INHIBITORY CONCN FOR MOST SUSCEPTIBLE PATHOGENS.
URINARY EXCRETION OF ... DOXYCYCLINE IS INCR @ HIGH URINARY PH VALUES. ALKALINE TREATMENT OF SUBJECTS RESULTED IN 24% INCR IN CUMULATIVE URINARY TETRACYCLINE EXCRETION COMPARED WITH ACID TREATMENT (P< 0.05) & 54% INCR FOR DOXYCYCLINE (P LESS THAN 0.05). RENAL CLEARANCE ... INCR DURING ALKALINE TREATMENT ... .
... MORE COMPLETELY ABSORBED AFTER ORAL ADMIN THAN OTHER TETRACYCLINES ... IN PLASMA, IT IS ABOUT 90% PROTEIN BOUND, WHICH IS HIGHEST DEGREE FOR ANY OF TETRACYCLINES.
It has been found that sugar acid salts represent beneficial controlled release forms for basic organic drug compounds. Examples of appropriate salts include mono, di, oligo and polysaccharide poly-O-sulphonic acid salts of antibiotics such as tetracyclins and aminoglycosides.
Carriers, Formulations, Methods For Formulating Unstable Active Agents For External Application And Uses Thereof
申请人：Foamix Ltd.
公开号：US20130189191A1
公开（公告）日：2013-07-25
The present disclosure teaches unique formulations for topical administration of tetracycline antibiotics, in which the tetracycline antibiotics remain stable.
CARRIERS, FORMULATIONS, METHODS FOR FORMULATING UNSTABLE ACTIVE AGENTS FOR EXTERNAL APPLICATION AND USES THEREOF
申请人：Tamarkin Dov
公开号：US20100310476A1
公开（公告）日：2010-12-09
The present disclosure teaches unique formulations for topical administration of tetracycline antibiotics, in which the tetracycline antibiotics remain stable.
