Bioavailability and pharmacokinetic characteristics of two monofluorophosphate preparations with calcium supplement

Two studies on the rate and extent of bioavailability of fluoride front a s ingle dose of oral preparations of sodium monofluorophosphate (Na2FPO3) com bined with calcium supplement were conducted according to a cross-over desi gn on 18 (Study 1) and 20 (Study 2) male healthy volunteers. respectively. Evaluated were: a) tablets containing 76 mg Na2FPO3 (Ref1); b) chewable tab lets containing 76 mg Na2FPO3 and 1250 mg calcium carbonate (Test1); c) eff ervescent tablets containing 76 mg Na2FPO and 3240 mg calcium lactogluconat e/carbonate (Ref 2); d) effervescent tablets containing 76 mg Na2FPO3 and 1 250 mg calcium carbonate (Test 2). In all preparations Na2FPO3 was equivale nt to 10 mg elemental F. The calcium supplement was equivalent to 500 mg el emental Ca. Fluoride was assayed in serum and in urine by a gas chromatogra phic method with a limit of quantitation of 10 ng/ml. Test1 was found equivalent to Ref1 with regard to rate and extent of bioava ilability of fluoride in serum. Test2 (effervescent tablets resulting in an oral solution of Na2FPO3 and ca lcium salts) was found bioequivalent in rate and extent to Ref2 (effervesce nt tablets authorized for marketing with the same content in F and Ca equiv alents as Test2). The pharmacokinetics of fluoride from all investigated pr eparations was characterized by a short lag time, a rapid absorption, a C-m ax of fluoride of 291-351 ng/ml (without significant differences between pr eparations) reached 30-75 min after administration, and a terminal t(1/2) o f 6-14 h. About 50 % of the absorbed fluoride was eliminated with the urine (from 0 to infinity time). The k(ur.el) was 0.06 h(-1) The renal clearance 65 ml/min. The preparations were well tolerated by the subjects. In conclusion, Test1 and Test2 represent combinations of Na2FPO3 with calci um supplement which are well tolerated and provide a rapid, reliable and pr actically complete bioavailability of fluoride. They are therefore suitable for the bone-forming therapy of osteoporosis.