HUMAN PHARMACOKINETICS OF ORALLY-ADMINISTERED STRONTIUM

Pharmacokinetics of orally administered SrCl2 (2.5 mmol), were studied in six healthy male volunteers. In the overall plasma concentration time (C-t) curves, two absorption phases were observed due to two dominant intestinal absorption loci. A method was devised to obtain separately the plasma C-t curves associated with each of the two absorption loci (curve 1 and curve 2). These curves and the overall plasma C-t curve were analyzed with a nonlinear estimation program (PCNONLIN). Pharmacokinetic parameters (mean±SD, n=6) calculated from the overall curve were as follows: peak plasma concentration (Cmax) 3.55±1.22 μg/ml and area under the plasma C-t curve (AUC∞) 9138±1930 μg·min/ml. The pharmacokinetic parameters calculated from curve 1 were as follows: terminal plasma elimination half-life time 47.3±7.9 hour, the plasma elimination half-life time of the preceding phase 5.2±3.3 hour, Cmax,1 3.09±0.95 μg/ml, the first-order absorption rate constant for absorption locus 1 (ka,1) 5.7±1.2×10-2 minute-1 and the time lag (tlag, 1) 11.7±7.9 minute. In three of the subjects the pharmacokinetic parameters of absorption locus 2 could be evaluated: ka,2=4.6±0.4×10-2 minute-1, tlag,2=77.3±4.0 minute, tmax,2=153±16 minute, Cmax,2=0.9±0.4μg/ml and AUC 2 ∞ =1204±565 μg·minute/ml. AUC 2 ∞ /AUC∞=0.14, indicating that 14% of the absorbed dose was absorbed via the second locus. The half-life time for the urinary strontium (Sr):creatinine ratio was 39.5±9.5 hour and the cumulative urinary excretion (day 0-6) was 34.0±13.8 mg, representing 15.5±6.3% of the administered dose and 84% of the estimated absorbed dose, respectively. The estimated bioavailability was 20% and the renal clearance (day 0-6) was lower than 4 ml/minute, indicating tubular reabsorption of Sr. © 1990 Springer-Verlag New York Inc.