title: Influence of plasma exchange on the disposition of the fourth generation cephalosporin cefepime.
abstract: Cefepime, a fourth generation cephalosporin, is widely used in hematology and oncology patients. These patients may require plasma exchange (PE) for indications such as chemotherapy- or cancer-induced thromobotic thrombocytopenic purpura to name a few. To date, no pharmacokinetic evaluation has been conducted assessing cefepime's disposition during PE. A 2 g IV cefepime single dose was given to patients undergoing therapeutic PE. Two hours from cefepime dose administration, plasma concentration was measured. PE was then instituted and cefepime plasmapheresate concentration was measured at the completion of the PE session. Cefepime levels were measured using HPLC. The percentage removed by PE was calculated as: amount removed/2 g dose. Ten adult patients were analyzed: median age (range): 52 years (33-67) and median weight (range); 82.85 kg (47-120). PE indications were: myasthenia gravis (n = 3), transverse myelitis (n = 2), multiple sclerosis (n = 1), chronic inflammatory demyelinating polyneuropathy (n = 1), idiopathic thrombocytopenic purpura (n = 1), thrombotic thrombocytopenic purpura (n = 1), and humoral rejection post cadaveric renal allograft (n = 1). All patients except one had a creatinine clearance >60 mL/min. One patient was excluded from the pharmacokinetic analysis owing to loss of venous access during PE. For the remaining nine patients, total plasma volume removed was 3.5 L (range: 2.5-3.5) and duration of PE was 120 min (range: 94-209). The cefepime removed by PE was 3.7% (range: 2.1-6.7). A strong correlation was found between cefepime plasma concentration prior to PE and the amount of drug removed (r = 0.96, r(2) = 0.92; p<0.05). The above results suggest that, under the studied conditions, cefepime removal by PE is clinically insignificant (approximately 4% of total 2 g dose).
authors.affiliation: Department of Pharmacy, Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201-2013, USA. ibrahim@karmanos.org
authors.forename: Rami B
authors.initials: RB
authors.lastname: Ibrahim
authors.forename: Chin Y
authors.initials: CY
authors.lastname: Liu
authors.forename: Simon M
authors.initials: SM
authors.lastname: Cronin
authors.forename: Bridgette C
authors.initials: BC
authors.lastname: Murphy
authors.forename: Raymond
authors.initials: R
authors.lastname: Cha
authors.forename: Paul
authors.initials: P
authors.lastname: Swerdlow
authors.forename: Tomoco
authors.initials: T
authors.lastname: Avila
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smith
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lewis
authors.forename: David J
authors.initials: DJ
authors.lastname: Edwards
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000378:metabolism; D010951:Plasma Exchange / Q000009:adverse effects*; D010956:Plasmapheresis
chemical_list: D000890:Anti-Infective Agents; D002511:Cephalosporins; D000077723:Cefepime; D003404:Creatinine