RELATIVE BIOAVAILABILITY OF EFFERVESCENT TABLET OF POTASSIUM CHLORIDE IN HEALTHY VOLUNTEERS

AIM To probe the approach by which the pharmacokinetics and relative bioavailability of endogenous medicinal substances can be studied. METHODS A randomized three-crossover study was performed in 18 healthy male volunteers. In two of the three study periods, a single 2 g dose of either effervescent tablet or common tablet of potassium chloride was administered; whereas in one of three periods no drug treatment was given to allow the nondrug-related (endogenous) potassium in urine to be determined. In each period the urine samples were collected at the following intervals: 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-24, 24-48 h after dose. Urine potassium was determined and the cumulative urine potassium-time data were fitted to a one-compartment model with first-order absorption. Bioavailability was represented by cumulative amount of potassium excreted in urine during 48 hours after drug administration and the bioequivalence of the two formulations was evaluated by analysis of variance and two one-sided t-test. RESULTS The pharmacokinetic parameters were as follows: effervescent tablet T_1/2ke=(6±5) h, T_1/2ka=(0.08±0.08) h,k_u=(0.09±0.04) h^-1,X_max/f=(18±8) mmol; common tablet T_1/2ke=(8±5) h, T_1/2ka=(0.11±0.11) h, k_u=(0.07±0.04) h^-1,X_max/f=(18±8) mmol. Relative bioavailability of effervescent tablet was 97.5%±15.2% compared with common tablet. CONCLUSION The two formulations were of bioequivalence. The methods used in this study might be applicable to other similar studies involving endogenous medicinal substances.