Metabolic Fate of [ ¹⁴ C]Cefamandole, a Parenteral Cephalosporin Antibiotic, in Rats and Dogs

Abstract

The biotransformation of the parenterally effective cephalosporin antibiotic cefamandole nafate (I) has been studied in rats and dogs. After rapid in vivo hydrolysis of the nafate pharmaceutical form to cefamandole (II), the antibiotic was found to be very resistant to metabolic degradation in both species. In dogs, cefamandole escaped metabolism and was eliminated as unaltered antibiotic almost exclusively by renal excretion. In rats, cefamandole was somewhat labile to metabolism; however, a major portion of the administered antibiotic was eliminated unchanged principally by renal excretion.

The cephalosporin antimicrobial agents: a comprehensive review

“…Urine concentrations of active drug are extremely high and bile levels are also high as long as no biliary obstruction exists. Cephalosporins penetrate poorly into prostatic tissue, occular humor, and, with a few exceptions, cerebrospinal fluid (Weliky et al, 1974;Naber & Madsen, 1976;Ryan et al, 1976;Sullivan et al, 1976Sullivan et al, , 1977Tsuchida et al, 1978;Waterman & Scharfenberger, 1978;Dingeldein & Wahlig, 1979;Murakawa et al, 1980;Komiya et al, 1981;Lunke el al., 1981;Studley el al., 1982;Williams el al., 1983;Klesel el al., 1984;DiPiro el al., 1985, Sakamoto el al., 1985Brown et al, 1986a and b;Fradet et al, 1986;Nightingale, 1986).…”

Pharmacokinetics of β-Lactam Antibiotics

“…Low levels were found in eye lens, brain, and spleen. Similar studies in dogs led to high levels of radioactivity in bile, kidney, and liver (SULLIVAN et al 1977).…”

“…It may be inferred from studies by SULLIVAN et al (1977) in rats and dogs that cefamandole, once formed by hydrolysis of its nafate precursor, does not undergo further metabolism in man.…”

Διείσδυση Νεώτερων Β-Λακταμικών Αντιβιοτικών Στην Κεφαλή Του Ανθρώπινου Μηριαίου Οστού

“…Oι Μέθοδοι με χρήση Ραδιενεργώς Σεσημασμένων Αντιβιοτικών (πχ 14C-Ceftazidime) και μετρητών σπινθηρισμών. [Sullivan, 1977], [Anderson, 1985] [Gouvas, 1988] -Παρασκευή Προτύπων Διαλυμάτων (Standards) Αντιβιοτικών: Τα υπό μελέτη αντιβιοτικά, Aztreonam, Ceftazidime, Cefamandol, χρησιμοποιήθηκαν υπό την ενέσιμη μορφή τους, σε φιαλίδια του 1g. Έτσι λοιπόν, η διαδικασία έχει ως εξής: Α. Ενίενται 10ml απεσταγμένου/αποστειρωμένου ύδατος(Α/Α), στο φιαλίδιο του 1g σκόνης αντιβιοτικού, και ανακινείται καλά.…”