The pharmacokinetics of furazlocillin in healthy humans. 1983

P H Hinderling, and U Gundert-Remy, and D Förster, and W Gau

The pharmacokinetics of the novel acylureidopenicillin furazlocillin, 6-[D-2-(3-furfurylidenamino-2-oxo-imidazolidine-1-carboxamido)-2 -(4-hydroxyphenyl)-acetamido]-penicillanic acid and of its penicilloic acid derivative were investigated in five healthy male volunteers after intravenous administration of 2 and 4 g dosages. The volunteers were either in a lying or sitting position throughout the duration of the studies. The concentrations of the drug in plasma and urine were measured by two different methods in parallel: a microbiological assay and a newly developed high pressure liquid chromatography method. The latter method was also applicable for quantitation of the penicilloic acid derivative in these biological fluids. The drug's plasma protein binding (66%) and apparent red cell-plasma partition coefficient (0.055) were concentration independent. The pharmacokinetics of the drug were first order only at the lower dose level. The apparent half lives of three distinguishable phases were, respectively, 4(t1/21), 18 (t1/22), and 64 (t1/2z) min. The total and renal clearances of the drug were, respectively, 303 and 79 ml/min. The latter value implied tubular secretion of the drug. Graphical and digital computer analyses of the data were performed with a linear three compartment body model. Small but consistent deviations from linear kinetics caused by the nonrenal elimination route were observed after administration of the higher dose (4 g). In contrast, renal elimination showed no such dose dependency and was first order. The disposition kinetics of furazlocillin were body position independent. The penicilloic acid derivative of furazlocillin was found in plasma and urine in all the five subjects tested. The percentage of the dose excreted renally as the derivative amounted, respectively, to 5.2 and 7.0% after the lower and higher dosage of furazlocillin, with significant inter- and intrasubject variability. The renal clearance of the derivative was 41 ml/min.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D010406 Penicillins A group of antibiotics that contain 6-aminopenicillanic acid with a side chain attached to the 6-amino group. The penicillin nucleus is the chief structural requirement for biological activity. The side-chain structure determines many of the antibacterial and pharmacological characteristics. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1065) Antibiotics, Penicillin,Penicillin,Penicillin Antibiotics
D011187 Posture The position or physical attitude of the body. Postures
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D001798 Blood Proteins Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins. Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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