title: Comparative pharmacokinetic analysis of latamoxef and CPW 86-363, a novel carboxy-pyrazol-cephalosporin and formation of N-methyl-thiotetrazole.
abstract: The pharmacokinetics of latamoxef and CPW 86-363, a novel carboxy-pyrazol-cephalosporin, were evaluated in healthy volunteers after intravenous bolus injection of 1 g. Based on concentration-time courses in serum both cephalosporins showed similar distribution properties, although CPW 86-363 was eliminated significantly faster. The route of elimination of latamoxef was mainly via the urine, whereas CPW 86-363 was also excreted into the bile. N-methylthiotetrazole, which is the common side chain in position 3 of both cephalosporins, was found in the serum as well as in the urine. Its rate and extent of formation was higher for latamoxef than for CPW 86-363 and depends rather on the instability of the parent compound than on metabolic transformation. This is supported by studies on the in vitro degradation of both derivatives. The relevance of these findings are discussed in view of secondary coagulopathies, which are associated with cephalosporins having a N-methylthiotetrazole side chain.
mesh_terms: D000328:Adult; D001393:Azoles / Q000378:metabolism*; D001711:Biotransformation; D001778:Blood Coagulation Disorders / Q000139:chemically induced; D002511:Cephalosporins / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D008297:Male; D009070:Moxalactam / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000378:metabolism*
chemical_list: D001393:Azoles; D002511:Cephalosporins; D013777:Tetrazoles; C038625:1-N-methyl-5-thiotetrazole; C052015:CPW 86363; D009070:Moxalactam