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Pharmacokinetics and protein binding of cefpiramide in patients with alcoholic cirrhosis
Author(s) -
DemotesMainard F,
Vinçon G,
Amouretti M,
Dumas F,
Necciari J,
Kieffer G,
Begaud B
Publication year - 1991
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1991.27
Subject(s) - cirrhosis , pharmacokinetics , regimen , alcoholic liver disease , medicine , urinary system , clinical pharmacology , gastroenterology , cephalosporin , drug , pharmacology , chemistry , antibiotics , biochemistry
The pharmacokinetics of cefpiramide, a new cephalosporin, were investigated after a single 1 gm intravenous injection in 11 patients with alcoholic cirrhosis and compared with those of 11 healthy subjects. In patients with cirrhosis the plasma elimination half‐life was three times longer than that in normal subjects. The total plasma clearance was decreased significantly (p < 0.001): 12.3 ± 6.5 ml/min in patients and 25.6 ± 4.6 ml/min in healthy volunteers, respectively. The urinary excretion of unchanged drug (percent of intravenous dose) for patients (69.8% ± 29.9%) was statistically higher (p < 0.01) than that for subjects (16.2% ± 3.9%). The renal elimination became increasingly important with hepatic impairment. Protein binding of cefpiramide was reduced significantly in the group with cirrhosis. The average unbound fraction was 10.4% ± 9.5% in patients with cirrhosis and 1.9% ± 0.3% in normal subjects (p < 0.01). Because the rate of elimination from plasma in patients is slower, the dosage regimen of cefpiramide would probably be modified in cirrhosis. Clinical Pharmacology and Therapeutics (1991) 49, 263–269; doi: 10.1038/clpt.1991.27