Clindamycin is partially metabolized to bioactive and inactive metabolites. The major bioactive metabolites are clindamycin sulfoxide and N-demethyl-clindamycin which are excreted in urine, bile, and feces. Within 24 hours, approximately 10% of an oral dose of clindamycin is excreted in urine and 3.6% is excreted in feces as active drug and metabolites; the remainder is excreted as inactive metabolites.
Only about 10% of the clindamycin admin is excreted unaltered in urine, and small quantities are found in feces ... Clindamycin is inactivated by metabolism to N-demethylclindamycin and clindamycin sulfoxide, which are excreted in the urine and bile.
Clindamycin has been linked to two forms of hepatotoxicity: transient serum aminotransferase elevations usually occurring after several days of high intravenous doses; and, an acute, idiosyncratic liver injury that arises within 1 to 3 weeks of starting therapy and is typically mild and self-limited.
High doses of intravenous clindamycin can be accompanied by elevations in serum ALT levels in the range of 2 to 10 times the upper limit of normal starting after 5 to 15 days of therapy in a manner similar to what occurs with intravenous oxacillin therapy (Case 1). Symptoms, jaundice, and alkaline phosphatase elevations are mild if they occur at all (Case 2), and aminotransferase levels rapidly fall into the normal range (in 1 to 2 weeks) upon stopping clindamycin or switching to lower doses or to oral formulations with which it rarely occurs.
Clindamycin therapy has also been linked to a clinically apparent, idiosyncratic liver injury that arises between 1 to 3 weeks after starting either oral or parenteral therapy (Case 3). The pattern of serum enzyme elevations is typically hepatocellular or mixed, but can be cholestatic. Allergic manifestations such as rash, fever and eosinophilia are typical, but often are not prominent and are not present in all cases. Autoantibodies are generally not present. The acute liver injury may accompany other signs of hypersensitivity such as Stevens Johnson syndrome or other severe skin reactions. The liver injury is usually mild-to-moderate in severity and resolves rapidly with stopping. However, fatal instances have been reported.
Likelihood score: B (highly likely cause of clinically apparent liver injury).
Concurrent use of kaolin- or attapulgite-containing antidiarrheals with oral clindamycin may significantly delay the absorption of oral clindamycin; concurrent use should be avoided or patients should be advised to take adsorbent antidiarrheals not less than 2 hours before or 3 to 4 hours after oral lincomycins.
Clindamycin has been reported to antagonize the bactericidal activity of aminoglycosides in vitro, and some clinicians recommend that these drugs not be used concomitantly. However, in vivo antagonism has not been demonstrated, and clindamycin has been administered successfully in conjunction with an aminoglycoside with no apparent decrease in activity.
Clindamycin is nearly completely absorbed following oral admin. Peak plasma concn of 2 to 3 ug/mL are attained within 1 hr after the ingestion of 150 mg. The presence of food in stomach does not reduce absorption. The half-life of the antibiotic is about 2.9 hr, and the modest accumulation of drug is thus expected if it is given at 6-hr intervals.
Clindamycin is widely distributed in many fluids and tissues, including bone. Significant concn are not attained in cerebrospinal fluid, even when the meninges are inflamed. Concn sufficient to treat cerebral toxoplasmosis are achievable .. The drug readily crosses the placental barrier. 90% or more of clindamycin is bound to plasma proteins. Clindamycin accumulates in polymorphonuclear leukocytes, alveolar macrophages, and in abscesses.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
半衰期在肾功能明显受损的患者中只会略微延长...
Half-life ... is lengthened only slightly in patients with markedly impaired renal function ...
Clindamycin is distributed into many body tissues and fluids including saliva, ascites fluid, pleural fluid, synovial fluid, bone, and bile. However, even in the presence of inflamed meninges, only small amounts of the drug diffuse into CSF. The concentration of clindamycin in synovial fluid and bone is reported to be 60-80% of concurrent serum concentrations of the drug; the degree of penetration does not appear to be affected by joint inflammation. Clindamycin readily crosses the placenta, and cord blood concentrations of the drug have been reported to be 46% of concurrent maternal blood concentrations. Clindamycin is distributed into milk.
来源:Hazardous Substances Data Bank (HSDB)
文献信息
Active agent loaded uniform, rigid, spherical, nanoporous calcium phosphate particles and methods of making and using the same
申请人：Laboratory Skin Care, Inc.
公开号：US10758478B2
公开（公告）日：2020-09-01
Uniform, rigid, spherical nanoporous calcium phosphate particles that define an internal space and an amount of active agent present in the internal space are provided. Also provided are topical delivery compositions that include the active agent loaded particles, as well as methods of making the particles and topical compositions. The particles and compositions thereof find use in a variety of different applications, including active agent delivery applications.
COMBINATION PREPARATIONS OF 3-N-FORMYLHYDROXYLAMINOPROPYL PHOSPHONIC ACID DERIVATIVES OR 3-N-ACETYLHYDROXYLAMINOPROPYL PHOSPHONIC ACID DERIVATIVES WITH CLINDAMYCIN AND ARTESUNATE
申请人：DMG Deutsche Malaria GmbH
公开号：US20220401462A1
公开（公告）日：2022-12-22
The present invention relates to pharmaceutical preparations containing as active ingredients 3-N-formylhydroxylaminopropylphosphonic acid derivatives or 3-N-acetylhydroxylaminopropylphosphonic acid derivatives in combination with clindamycin and artesunate for the treatment of malaria, in particular for the acute therapy of cerebral malaria, and to an associated dosage, in particular for the patient group of children.
