Glycerophosphate Is Interchangeable with Inorganic Phosphate in Terms of Safety and Serum Pharmacokinetics

Abstract

Objective: The primary aim of the present investigation was to determine and compare the pharmacokinetic (PK) profiles of inorganic phosphate in serum and urine after intravenous administration of sodium glycerophosphate and inorganic sodium phosphate. Additionally, study product safety profiles were evaluated. Subjects and Methods: In total, 27 healthy, white volunteers (17 male/10 female) were enrolled in this double-blinded, randomized, 2-sequence, crossover study and were assigned to receive an organic test drug (sodium glycerophosphate) and an inorganic reference preparation (sodium phosphate) on 2 occasions. Validated analytical methods were used, and concentrations of total inorganic phosphate in serum and urine were determined over 24 h following a single 4-hour continuous intravenous infusion of test and reference drugs at a dose of 80 mmol. Study days were separated by washout periods of 7 days. An analysis of variance, based on population means and 90% confidence intervals (CIs), was used for testing bioequivalence (BE; range 0.8–1.25) between investigational products. Results: The geometric means of the ratio of the point estimates and corresponding 90% CIs for the area under the concentration-versus-time curve of inorganic serum phosphate from 0 to 24 h (AUC_0–24), the phosphate’s maximum concentration in serum (C_max) and the total amount of inorganic phosphate excreted in urine over 24 h corrected for individual baseline values (Ae_{0–24 bc}) were estimated. The test/reference ratios for inorganic phosphate were 1.04 (CI 1.00–1.07), 0.85 (CI 0.84–0.87) and 0.84 (CI 0.77–0.92) for AUC_0–24, C_max in serum and Ae_{0–24 bc} in urine, respectively. Hence, standard BE criteria were met for AUC_0–24 and C_max in serum, while Ae_{0–24 bc} marginally failed to demonstrate BE. After drug administration, a total of 15 subjects reported the occurrence of at least 1 treatment emergent adverse event (AE). All AEs were classified as mild to moderate in severity, and the two treatment groups were equally affected. No serious AEs occurred. Conclusion: The serum PK profiles of inorganic phosphate were almost superimposable following intravenous administration of equimolar doses of test and reference drugs. Thus, we conclude that the two study drugs are essentially similar in terms of serum PK profiles, safety and tolerability.