Pharmacokinetics of betamethasone and betamethasone 17-monopropionate in Chinese healthy volunteers after intramuscular injection of betamethasone phosphate/betamethasone dipropionate

Abstract

The aim of this study was to evaluate the pharmacokinetic profiles of betamethasone (BOH, CAS 378-44-9) and betamethasone 17-monopropionate (B17P), the active metabolites of betamethasone phosphate (BSP) and betamethasone dipropionate (BDP), respectively, after administration of betamethasone i. m. (BSP 2 mg and BDP 5 mg). After ten healthy volunteers had received a singledose intramuscular adminitration of betamethasone i. m., blood samples were collected pre-dose and for 336 h postdose. The plasma levels of B17P and BOH were measured by liquid chromatography-tandem mass spectrometry (LC-MS/ MS). When compared to ΒΟΗ, Β17Ρ exhibited a longer time to maximum concentration (15.0 ± 9.0 h vs. 2.8 ± 1.7 h), a lower C_max (0.6 ± 0.2 ng/mL vs. 14.5 ± 3.7 ng/mL), and a much longer half-life (80.8 ± 22.7 h vs. 9.6 ± 3.6 h). Betamethasone i. m. produced rapid onset and sustained action through an initial rapid-increased plasma concentration of BOH and a sustained plasma concentration of B17P, respectively.

Key words

Betamethasone - Betamethasone dipropionate - Betamethasone 17-monopropionate - Intramuscular administration - Pharmacokinetics

• References

• 1 Diprospan Injection 1 × 1 ml Amp. http://all-drugs-online.com/Drugs/Glucocorticoid/9580.aspx Accessed September 22, 2010.
• 2 Wurthwein G, Rehder S P R. Lipophilicity and receptor affinity of glucocorticoids. Pharm Zgt Wiss 1992; 137: 161-7
• 3 Moss TJ, Doherty DA, Nitsos I, Harding R, Newnham IP. Pharmacokinetics of betamethasone after maternal or fetal intramuscular administration. Am J Obstet Gynecol 2003; 189: 1751-7
• 4 Ballabh P, Lo ES, Kumari I, Cooper TB, Zervoudakis I, Auld PA et al. Pharmacokinetics of betamethasone in twin and singleton pregnancy. Clin Pharmacol Ther 2002; 71: 39-45
• 5 Petersen MC, Nation RL, McBride WG, Ashley JJ, Moore RG. Pharmacokinetics of betamethasone in healthy adults after intravenous administration. Eur J Clin Pharmacol 1983; 25: 643-50
• 6 Samtani MN, Lohle M, Grant A, Nathanielsz PW, Jusko WJ. Betamethasone pharmacokinetics after two prodrug formulations in sheep: implications for antenatal corticosteroid use. Drug Metab Dispos 2005; 33: 1124-30
• 7 Samtani MN, Schwab M, Nathanielsz PW, lusko WJ. Stabilization and HPLC analysis of betamethasone sodium phosphate in plasma. J Pharm Sci 2004; 93: 726-32
• 8 Zou JJ, Dai L, Ding L, Xiao DW, Bin ZY, Fan HW et al. Determination of betamethasone and betamethasone 17monopropionate in human plasma by liquid chromatography-positive/negative electrospray ionization tandem mass spectrometry. J Chromatogr B 2008; 873: 159-64
• 9 Petersen MC, Nation RL, Ashley JJ. Simultaneous determination of betamethasone, betamethasone acetate and hydrocortisone in biological fluids using high-performance liquid chromatography. J Chromatogr 1980; 183: 131-9
• 10 Hirano K, Ichihashi T HY. Studies on the absorption of practically water-insoluble drugs following injection. II. Intramuscular absorption from aqueous suspensions in rats. Chem Pharm Bull (Tokyo) 1981; 29: 817-27
• 11 Zuidema J, Kadir F, Titulaer HAC, Oussoren C. Release and absorption rates of intramuscularly and subcutaneously injected pharmaceuticals (II). Int J Pharm 1994; 105: 189207-
• 12 Daley-Yates PT, Price AC, Sisson JR, Pereira A, Dallow N. Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man. Br J Clin Pharmacol 2001; 51: 400-9
• 13 Betts A, Atkinson F, Gardner I, Fox D, Webster R, Beaumont K et al. Impact of physicochemical and structural properties on the pharmacokinetics of a series of alphalLadrenoceptor antagonists. Drug Metab Dispos 2007; 35: 1435-45