Microdosing vs. Therapeutic Dosing for Evaluation of Pharmacokinetic Data: A Comparative Study

Objectives: Human microdosing studies or phase 0 studies have been proposed to supplement pharmacokinetic (PK) studies in animals. In phase 0 studies, extremely low, nonpharmacologically active doses of a drug are given to a few subjects before phase 1, to deÞ ne the agent’s PK proÞ le in humans. This study has been conducted to compare the values of different PK parameters, as determined by microdosing and conventional therapeutic dose studies in healthy volunteers, and target patient population. Materials and Methods: In the Þ rst phase of study, 30 healthy adult male volunteers were divided into three groups of 10 each; receiving 14C-labelled atenolol, enalapril and losartan orally, in single microdose. After a wash-out period of 10 days, the same individual received the same drug in single therapeutic dose. In second phase of study, 30 hypertensive patients were divided into three groups and given same drugs. Parameters studied were t½, AUC, Cmax and tmax. Blood samples collected at intervals were subjected to accelerator mass spectrometry (AMS) and high performance liquid chromatography (HPLC), for microdosing and therapeutic dose studies respectively. Results: Microdosing results were comparable with therapeutic dose values for all the drugs studied and showed linearity over therapeutic dose. Conclusions: Microdosing PK parameters are comparable to the ones determined by therapeutic dose studies up to a permissible limit. So the idea of phase 0 PK studies supplementing phase 1 PK studies can be furthered.