Comparative pharmacokinetics and pharmacodynamics of furosemide in Middle Eastern and in Asian subjects.

The pharmacokinetics and pharmacodynamics of a single oral dose of 40 mg furosemide has been compared in 11 healthy Middle Eastern Arabs with 12 Asian subjects under fasting conditions. There were no significant differences (p > 0.05) between the 2 ethnic groups in either the area under the plasma concentration time curve (AUC) or the time to maximal plasma concentration (tmax). The elimination half-life was significantly higher (p < 0.05) in Middle Eastern subjects (2.9+/-0.7 h) than in Asian subjects (2.2+/-0.6 h), while the maximal plasma concentration (Cmax) in Asian subjects (1,087+/-262 ng/ml) was significantly higher (p < 0.05) compared with Middle Eastern Arabs (776+/-163 ng/ml). The mean residence time (MRT) and the operative apparent volume of distribution (Vd/F) were significantly greater in Middle Eastern Arabs (4.5+/-0.9 h and 54.1+/-14.91) than in Asian subjects (3.6+/-0.8 h and 38.6+/-16.51). The difference between them in (Vd/F) abolished (p > 0.05) when corrected for body weight. The mean cumulative urinary excretion of furosemide in 8 h was 5.6 mg (range 1.6-15.2 mg) for Arabs and 6.1 mg (range 2.1-15.9 mg) for Asians. The relationships between furosemide-induced diuresis and furosemide, sodium, potassium, calcium, magnesium and chloride excretion rates appeared as a clockwise hysteresis loop indicating the development of tolerance during the course of drug action in both ethnic groups. No statistically significant differences (p > 0.05) were observed in the cumulative amounts excreted in urine of these electrolytes or their excretion rates between Arabs and Asians. The relationships between urinary excretion rates of sodium, potassium, calcium, magnesium, and chloride were linear with almost identical slopes for Arabs and Asians in each relationship.