[Use of a physiological model of gentamicin pharmacokinetics for individual dosage of the antibiotic].
A new approach to fixing the initial doses of gentamicin (GM) for its intramuscular administration (the most commonly used anyway) is discussed. The approach is based on the physiological model reproducing the individual patterns of GM concentration change in patient's blood. Such parameters of the model as blood flow velocity and actual average volume of specific tissues as well as the tissue to the blood partition coefficient (Kp) are constant. They were used to calculate the volume of distribution in the body specific organs (Vs). The apparent distribution volume (Vd) and total clearance (Cl) are individual parameters. The Vd value was calculated individually for every particular patient depending on the body weight by the known equations. The difference between Vd and Vs was used to calculate the individual Kp for the organs and tissues which were not specially examined. When calculating Cl of GM, the patient's sex, age, weight and creatinine concentrations were taken into account. To evaluate the local velocity of blood flow after antibiotic intramuscular administration, it was important to consider the patient's sex and age. The approach was used to reproduce the individual patterns of GM concentration change after the initial administration of the antibiotic, 80 mg, to 19 male patients (age range, 21 to 73 years; weight range, 50 to 94 kg; blood creatinine concentration, 0.4 to 1.6 mg/dl). The GM concentrations attained with the use of the model were afterwards compared to the data on FPIA. (TDx, Abbott) by measuring the GM concentrations in the blood of the patients 0.5, 1, 5 and 7 hours after the administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Manuĭlov
K K
KK
Kuleshov
S E
SE
Obolonkov
V Iu
VIu
Liubovina
A B
AB
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005839:Gentamicins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D013997:Time Factors; D014018:Tissue Distribution
D005839:Gentamicins
Ispol'zovanie fiziologicheskoĭ modeli farmakokinetiki gentamitsina dlia individual'nogo dozirovaniia antibiotika.