Development of a new method for bioavailability assessment using a pharmacokineic/pharmacodynamic model

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The rapid development of automated synthetic and recombinant DNA methods of peptide preparation have made available a great variety of peptide and peptide analogs of potential therapeutic value. Example include synthetic peptide hormons (such as insulin, vasopressin, calcitonin, somatostatin, etc.), peptide analogs, renin inhibitors, and angiotensin converting enzyme inhibitors are currently available for clinical use. The usual route of adsministration of these compounds were intravascular, intramuscular or subcutaneous ; however, a number of side effects due to injection have been reported. Although, oral, rectal or nasal route have attracted ateension, because of its potential to improve the side-effects, the assesment of bioavailability after extravascular administration of these drugs are extremely difficult. The objective of this project is to develop a new method for bioavailability assessment and to optimise the dosage regimens after oral nasal administration of these drugs. Captopril (CP), salmon calcitonin (sCT) and arginine vasopressin (AVP) were used as model compounds. A pharmacokinetic (PK) / pharmacodynamic (PD) model, including physiological regulation systems, such as arterial pressure control system, plasma calcium regulation system and/or urinary sodium regulation system was constructued, and the pharmacological data after extravascular administraiton of these drugs were analyzed. Results indicated that the rate and extent of bioavailability of these drugs were precisely estimated by the PK/PD model.