Human pharmacokinetics of orally administered strontium

Summary

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 (C_max) 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, C_max,1 3.09±0.95 μg/ml, the first-order absorption rate constant for absorption locus 1 (k_a,1) 5.7±1.2×10⁻² minute⁻¹ and the time lag (t_{lag, 1}) 11.7±7.9 minute. In three of the subjects the pharmacokinetic parameters of absorption locus 2 could be evaluated: k_a,2=4.6±0.4×10⁻² minute⁻¹, t_lag,2=77.3±4.0 minute, t_max,2=153±16 minute, C_max,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.