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  • Title: [Pharmacokinetic basis for antibiotic therapy in broncho-pulmonary bacterial infections (author's transl)].
    Author: Grosset J, Bismuth R, Nguyen J.
    Journal: Rev Fr Mal Respir; 1982; 10(3):195-203. PubMed ID: 7111829.
    Abstract:
    Pharmacokinetics is the study of the absorption, distribution and elimination of a drug in the body. Applied to antibiotic therapy it gives information on the concentrations of antibiotic that reach the bacteria at a given time at their site of multiplication for a given dose and route of administration. The future of an antibiotic within a body is largely related to passive transfer. This can be compared to the dialysis of molecules across a semi-permeable membrane, the passage from one side to the other being a function of the concentration of molecules in the "upstream" side, the size of the molecules and their own particular transfer speed. The final result is affected by 1) the partition coefficient itself related to the degree of aqueous and lipid solubility of the molecules, 2) the degree of ionisation of the molecules, non-ionised molecules being the only ones to be transferred, 3) protein binding as only the unbound fraction is biologically active and capable of diffusing across the membranes, 4) by the interplay of the combined phenomena of resorption, distribution and elimination. Penicillins and macrolides are the antibiotics of choice in broncho-pulmonary infections. The tetracyclines and the sulfamethoxazole-trimethoprim combination come second. The combination of a beta-lactam, an aminoglycoside and/or metronidazole are reserved for the most severe infections. The lung is a particularly well vascularised organ, the pulmonary concentrations of the antibiotic may equal the serum levels. But the concentration in the bronchial secretions only reaches 55% of the serum levels for clindamycin, 25 to 30% for aminoglycosides, minocycline and bacampicillin, 20% for cephalosporins and doxycycline and less than 10% for ampicillin and erythromycin. Only oleandomycine, spiramycin and trimethoprim are present in concentrations equal to those in the serum.
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