Use of gentamicin physiologically-based model for individual dosing. 1993

K K Manuilov, and S M Navashin, and S E Kuleshov
National Research Centre of Antibiotics, Moscow, Russia.

A new approach to fixing initial doses of gentamicin (GM) for i.m. administration (that is most commonly used anyway) is discussed. This approach is based on a physiologically-based model allowing to reproduce individual patterns of GM concentration change in the patient's blood. This approach was used to reproduce the individual pattern of GM concentration change after the initial i.m. administration of 80 mg to 19 male patients (age-range 21 to 73 years, weight range 50-94 kg, creatinine concentration in the blood 0.4-1.6 mg/d). The GM concentration levels, obtained with the help of this model, were afterwards compared to the results of FPIA measurement of GM concentrations in the blood of the patients 0.5, 1, 2, 3, 5 and 7 h after administration. It proved that the average deviation of the predicted values from the actual was equal to 20 per cent for all the measuring time-points. For comparison we used individual patterns of GM distribution in blood calculated according to the one-compartment model from the same values of Vd, Cl and dose. In this case the error of pharmacokinetic prediction exceeded the 20 per cent and amounted to 43 per cent by 0.5 and 7 hours. Thus, the new approach with the physiologically-based model provides better accuracy for stable pharmacokinetic prediction for longer stretches of time upon administration, which is especially important for the correct establishment of dosing intervals.

UI MeSH Term Description Entries
D007273 Injections, Intramuscular Forceful administration into a muscle of liquid medication, nutrient, or other fluid through a hollow needle piercing the muscle and any tissue covering it. Intramuscular Injections,Injection, Intramuscular,Intramuscular Injection
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D003404 Creatinine Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D005839 Gentamicins A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS. Gentamicin Sulfate (USP),Gentamycin,G-Myticin,Garamycin,Gentacycol,Gentamicin,Gentamicin Sulfate,Gentamycins,Gentavet,Genticin,G Myticin,GMyticin,Sulfate, Gentamicin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D016903 Drug Monitoring The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. Monitoring, Drug,Therapeutic Drug Monitoring,Drug Monitoring, Therapeutic,Monitoring, Therapeutic Drug

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