Urodynamic modeling of norfloxacin pharmacokinetics by means of computer simulation

Urodynamic model was developed which, in conjunction with a compartmental pharmacokinetic model, was used for study of factors influencing drug concentrations in urine: urine flow rate, residual bladder urine, maximal bladder urine, stage of renal failure, and elimination kinetics of drugs. Norfloxacin (NOR) was used as a model drug, although the model haw general applicability for all urinary antiseptics. Pharmacokinetic data were obtained from a clinical study in which norfloxacin was administered orally as a single 400mg dose to four subjects with installed urine catheters. Sample of blood, bladder and catheter urine were collected and concentrations of NOR measured by a HPCL method. Modeling was performed on analog--hybrid computer EAI 580. Besides the fitting of model response to obtained in vivo data, simulations of expected clinical situations were performed in which the interplay of above mentioned factors was studied in terms of urine concentrations profiles. NOR treatment with 400mg b.i.d. secured sufficient urine concentrations in most studied cases. This approach should be applied for corresponding study of other urinary antiseptics, especially those with less favourable urinary levels.