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crabmonkey新蟲 (初入文壇)
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[求助]
鹽酸頭孢替安酯 藥理毒理
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癡夷子皮
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【答案】應(yīng)助回帖
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感謝參與，應(yīng)助指數(shù) +1
mouse103: 金幣+2, 辛苦 2012-04-19 20:55:13
感謝參與，應(yīng)助指數(shù) +1
mouse103: 金幣+2, 辛苦 2012-04-19 20:55:13
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Absorption Bioavailability Intramuscular: 60% to 86% (Brisson et al, 1984) Oral: 45.5% (Korting et al, 1990) Distribution Distribution Sites Protein Binding 40 to 62% (Wise et al, 1981; Brogard et al, 1989). OTHER DISTRIBUTION SITES Amniotic Fluid: A single 1 gram IV cefotiam dose produced peak levels of 19.6 to 23.5 mcg/mL in amniotic fluid approximately 2.5 hours after IV infusion to the mother (Miyakawa et al, 1984). BILE Mean cefotiam concentrations of 17.4 micrograms/milliliter (mcg/mL) and 31.8 mcg/mL occurred in the gallbladder bile and gallbladder wall, respectively, 30 minutes after the intravenous administration of cefotiam 1 gram to 7 patients with cholelithiasis. Cefotiam concentrations in the hepatic bile were 1177, 1115, and 149 mcg/mL measured in 3 of the 7 patients (Satake et al, 1982). One hour following the administration of cefotiam 1 g IV to 10 patients undergoing cholecystectomy the drug concentrations in the choledochal and gallbladder bile were 502 and 140 mcg/mL, respectively (Brogard et al, 1986). Drug levels were determined by antibiotic activity using the agar plate diffusion method. In 4 patients with obstructive jaundice, the mean concentration of cefotiam in the hepatic bile was 19.5 mcg/mL 1 hour after the IV administration of cefotiam 1 gram (Satake et al, 1982). Six hours later, the concentration dropped to 5.9 mcg/mL. BONE MARROW A single IV dose of cefotiam 2 g produced bone marrow concentrations of 76.1 and 44.4 mcg/mL after 0.5 and 1 hour, respectively, after administration (Yamamura et al, 1983). Measurements were made by high-performance liquid chromatography. BRONCHIAL SECRETIONS A single IV cefotiam 1 gram dose produced a mean peak bronchial secretion concentration of 5.8 mcg/mL 4 hours after the end of infusion in 15 patients with an exacerbation of chronic bronchitis or bronchiectasis (Bergogne-Berezin et al, 1982). The range of cefotiam concentrations was 0.7 to 10 mcg/mL in bronchial secretions from 1 to 4 hours after the end of infusion. UMBILICAL CORD A single 1 gram IV cefotiam dose produced peak levels of 13 to 23.9 mcg/mL in umbilical cord blood between 15 and 30 minutes after IV infusion to the mother (Miyakawa et al, 1984). The ratio of the cefotiam concentration in fetal blood to maternal blood ranged from 0.75 to 1.3 during the 1 to 3 hours following IV administration. WOUND FLUID Cefotiam 2 g IV had a peak wound fluid concentration of 22.5 mcg/mL which occurred 6 hours after administration to 5 patients undergoing mastectomy and dissection of the axillary lymph nodes (Ueda et al, 1985). The ratio of peak wound fluid to serum concentrations was 29.3%. BLISTER FLUID Cefotiam 400 mg orally provided maximum serum concentrations of 2.6 mcg/mL at 2.1 hour and 0.9 mcg/mL in blister fluid (Korting et al, 1990). The cefotiam concentrations in blister fluid were close to MIC90 of Staph aureus, S epidermidis, H influenzae, and exceeded MIC90 of Streptococci, E coli, and Proteus mirabilis. The oral administration or cefotiam 400 mg TID should be curative in the majority of bacterial infections of skin and soft tissues. Distribution Kinetics Distribution Half-Life 3 to 7 minutes (Rouan et al, 1985). Volume of Distribution 0.5 liters/kilogram (Brisson et al, 1984). Excretion Kidney Renal Clearance (rate) In patients with renal insufficiency (creatinine clearance 3 to 10 mL/min), the renal clearance of IV cefotiam 1 g was 3.3 mL/min (Lecaillon et al, 1984a). A calculated renal clearance following intravenous cefotiam 0.5, 1 and 2 grams was 16, 13.3 and 11.3 liters(L) per hour, respectively in 3 healthy volunteers. The total plasma clearance was calculated to be 26.8, 22.8 and 17.8 L/hour, respectively with total plasma clearances varying from 19.6 to 22.5 L/hour (Brisson et al, 1984; Rouan et al, 1985). Renal Excretion (%) 50% to 67% (Brisson et al, 1984; Daschner et al, 1982). Between 50% to 67% of an intravenous cefotiam dose was excreted unchanged in the urine of healthy volunteers (Brisson et al, 1984; Daschner et al, 1982). In patients with renal insufficiency (creatinine clearance 3 to 10 mL/min), only 13% of the administered cefotiam dose was excreted unchanged in the urine (Lecaillon et al, 1984a). Other OTHER EXCRETION Bile, 1.8% to 3.6% (Terziivanov et al, 1986; Brogard et al, 1986). Total biliary excretion of cefotiam was 0.2% of the dose in 7 patients with cholelithiasis (Satake et al, 1982). Approximately 1.8% to 3.6% of an administered cefotiam dose was recovered over 12 hours in the bile of cholecystectomy patients (Terziivanov et al, 1986; Brogard et al, 1986). Cefotiam had a biliary clearance of 11.8 mL/min in 6 patients after undergoing a cholecystectomy (Terziivanov et al, 1986). Elimination Half-life Parent Compound ELIMINATION HALF-LIFE 0.6 to 1.1 hours (Daschner et al, 1982) Cefotiam half-life was 54, 68 and 98 minutes following intravenous bolus doses of 0.5, 1 and 2 grams, respectively in 3 healthy volunteers (Rouan et al, 1985). Cefotiam pharmacokinetics appear to be dose dependent, with increasing half-lives with increasing doses. Calculated half-lives were 0.6 hours for 0.5 gram doses to 1.1 hours for a 2 gram dose in 8 healthy volunteers (Daschner et al, 1982). Patients with RENAL INSUFFICIENCY (creatinine clearance 3 to 10 mL/min) had a cefotiam half-life of 5.3 hours (Lecaillon et al, 1984a). Extracorporeal Elimination Hemodialysis Dialyzable: Yes (Konishi & Ozawa, 1984a). Approximately 44% of the administered dose of cefotiam is recovered in the total pooled dialysate outflow fluid (Konishi & Ozawa, 1984a). The average hemodialysis clearance of cefotiam was calculated to be 40.5 mL/min with a mean half-life of 2.7 hours. This study was conducted in 4 terminal renal failure patients on intermittent dialysis. Cefotiam 1 gram was administered into the venous return of the dialyzer over 5 minutes immediately after the start of dialysis. The patients were dialyzed for 5 hours at a constant dialysis flow rate of 500 mL/min and a constant blood flow rate of 200 mL/min. Similar half-lives and dialysate recovery percents are reported (Lecaillon et al, 1984a). Peritoneal Dialyzable: No (Brouard et al, 1988a). Only 6% of an 1 g cefotiam dose was recovered in the dialysate during a 5-hour dwell of continuous ambulatory peritoneal dialysis (Brouard et al, 1988a). Hemofiltration Dialyzable: Yes (Evers et al, 1993; Alonso et al, 1986). In 5 patients, 27% to 60% of cefotiam was removed in 24 hours by continuous haemofiltration (Evers et al, 1993; Alonso et al, 1986). Cefotiam 1 gram twice daily should provide effective therapy for septic patients with renal failure undergoing continuous arterio-venous or veno-venus haemofiltration. Hemofiltration of cefotiam produced an extraction ratio of 0.25 and a hemofiltration clearance of 74 mL/min in 5 patients with terminal renal failure (Alonso et al, 1986). Cefotiam 1 gram was administered as an IV bolus immediately before hemofiltration. Filtration lasted for 4 hours at blood flow rate of 300 mL/min with the volume of filtrate ranging between 14 and 20 L. |
2樓2012-04-19 13:40:43
癡夷子皮
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Cardiovascular Effects Thrombophlebitis PHLEBITIS and thrombophlebitis have been reported in approximately 6% of patients receiving IV cefotiam (n=79) (Ishigami et al, 1981a); (Beumer et al, 1985)(Lentino et al, 1984a). Dermatologic Effects Dermatological finding Summary Several case reports of CONTACT DERMATITIS and contact urticaria have been reported in nurses preparing IV solutions of cefotiam (Miyahara et al, 1993); (Tadokoro et al, 1994 Shimizu et al, 1996). Rashes have also been reported in patients receiving cefotiam (Ishigami et al, 1981, Letino et al, 1984)(Bailey et al, 1982a). Mild rashes have been reported with intravenous (IV) cefotiam therapy (Ishigami et al, 1981a); (Letino et al, 1984). A severe RASH developed in a 20-year-old woman after 2 doses of IV cefotiam for a urinary tract infection (Bailey et al, 1982a). Contact urticaria with hand eczema from cefotiam is described in nurses (Chiba et al, 1999; Miyahara et al, 1993). Cefotiam was the common causative agent in 13 case reports in the last 10 years in Japan (Miyahara et al, 1993). One nurse also developed systemic symptoms of cough, nausea, abdominal pain, and diarrhea (Chiba et al, 1999). Contact ANAPHYLAXIS induced by cefotiam is described. Both patients had hand dermatitis that had appeared and preceded the episodes of anaphylaxis (Tadokoro et al, 1994). It seemed most likely that it was induced or exacerbated by cefotiam and facilitated the penetration of cefotiam to cause the anaphylaxis (Tadokoro et al, 1994). A patient with gradually worsening hand eczema and atopic dermatitis experience severe itching followed by loss of consciousness after cefotiam solution accidentally splashed into her mouth. Skin test was positive for cefotiam but negative for several other cephalosporins and beta-lactams (Shimizu et al, 1996). Injection site pain Mild pain on injection has been reported with intravenous cefotiam therapy in a similar occurrence rate as seen with intravenous cefamandole therapy (Beumer et al, 1985). Hematologic Effects Factor II deficiency Intravenous cefotiam has been associated with hypoprothrombinemia (de Miguel et al, 1991). Neutropenia A 12-month-old boy was given cefotiam 100 milligrams/kilogram for 5 days for pneumonia. Four days later, he had neutropenia (2% neutrophils). Cefotiam was discontinued, but asymptomatic neutropenia persisted. Assays for antibodies to various viruses were negative. The neutropenia persisted and was shown to be autoimmune in nature. As granulocyte-bound IgG decreased over the next 11 months, absolute neutrophil counts increased. The authors suggested that the persistent autoimmune neutropenia was triggered by the antibiotic (Taniuchi et al, 2000). Hepatic Effects Hepatotoxicity Transient ELEVATED LIVER ENZYMES including glutamic oxalacetic and pyruvic transaminase, and alkaline phosphatase have been reported during cefotiam therapy (Ishigami et al, 1981a; Lentino et al, 1984a). Levels returned to normal shortly after therapy discontinuation. Immunologic Effects Immune hypersensitivity reaction Summary Several case reports of contact dermatitis and contact URTICARIA have been reported in nurses preparing IV solutions of cefotiam (Miyahara et al, 1993); (Tadokoro et al, 1994 Shimizu et al, 1996). Cefotiam was the common causative agent in 13 case reports in the last 10 years in Japan (Miyahara et al, 1993). Contact ANAPHYLAXIS induced by cefotiam is described. Both patients had hand dermatitis that had appeared and preceded the episodes of anaphylaxis (Tadokoro et al, 1994). It seemed most likely that it was induced or exacerbated by cefotiam and facilitated the penetration of cefotiam to cause the anaphylaxis. A patient with gradually worsening hand eczema and atopic dermatitis experience severe itching followed by loss of consciousness after cefotiam solution accidentally splashed into her mouth. Skin test was positive for cefotiam but negative for several other cephalosporins and beta-lactams (Shimizu et al, 1996). |
3樓2012-04-19 13:41:25
癡夷子皮
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4樓2012-04-19 13:41:59
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