Author/Editor		Mrhar, A; Primožič, S; Kozjek, F; Karba, R; Drinovec, J
Title		Modeling and simulation of specific physiologic and pathologic conditions of drug elimination organs
Type		članek
Source		Acta Pharm Jugosl
Vol. and No.		Letnik 40, št. 2, Suppl 1
Publication year		1990
Volume		str. 263-78
Language		eng
Abstract		Effective treatment of urinary tract infections depends upon provision of adequate levels of antibacterial agent in the lower and upper part of urinary tract. Besides the elimination kinetics of drugs, physiologic factors such as urine formation rate, residual and maximal bladder volume, and fequency of mucturitions play an important role in securing therapeutic levels of the drug. The aims of the present study were the evaluation of interplay of above mentioned physiologic and pharmacokinetic factors, and the assessment of their importance for the optimal therapy design. On the basis of clinical pharmacokinetic study of norfloxacin, modeling was performed in order to develop an appropriate pharmacokinetic-urodynamic model using analog-hybrid simulation as a tool. The results of the study show that in the case of norfloxacin, which was given in 400 mg dose every 12 hours, even in infavourable cases of urinary tract dynamics, i.e. low elimination rate of norfloxacin, high residual volume and low maximal volume of the bladder urine, levels of the drug are preserved in the bladder and ureteral urine, which are well above the MIC values for susceptible microorganisms. Hemodialysis, continuous ambulatory peritoneal dialysis and plasmepheresis are clinical procedures used for the treatment of patients with end-stage renal failure. When drug therapy is indicated the individual treatment of those patients is necessary. The work deals with the employment of compartmental modeling for the study of drugs pharmacokinetic in mentioned conditions using analog-hybrid simulation. Through the process of model development and validation by the aid of the results of corresponding in vivo studies, the suitable multicompartment models with linear and nonlinear character and time varying parameters were obtained. They enable dosage regimen and therapy optimization, taking into account all expected limitations.(trunc.)
Descriptors		COMPUTER SIMULATION MODELS, BIOLOGICAL URODYNAMICS URINARY TRACT NORFLOXACIN KIDNEY FAILURE, CHRONIC HEMODIALYSIS PLASMAPHERESIS CIPROFLOXACIN