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.

Glycerophosphate Does Not Interact with Components of Parenteral Nutrition

“…This approach allowed us to obtain a more detailed understanding of the behavior of serum phosphate PKs during test and reference drug administration and also provided the opportunity to verify whether these differences are statistically significant. This additional, out of protocol PK analysis confirmed previous findings of bioequivalence between treatments for the AUC 0-8 , AUC [8][9][10][11][12][13][14][15][16] and AUC 16-36 time fragments. However, the test/reference ratio of the total amount of phosphate in urine collections over 24 h missed the lower bioequivalence boundary, leading to the assumption that urine collections over 24 h are of limited value for the determination of phosphate bioequivalence assessment.…”

“…In separate experiments, we were able to demonstrate that the serum PK profiles of inorganic phosphate are super-imposable for sodium glycerophosphate and pure inorganic phosphate solution after intravenous administration of equimolar doses to healthy volunteers [9] . The hydrolytic conversion of glycerophosphate to inorganic phosphate is a fast process.…”

Significant Published Articles for Pharmacy Nutrition Support Practice in 2016

“…Studies have shown that NaGP has a more favorable serum pharmacokinetic profile and a lower propensity to precipitate with the divalent calcium ion compared with inorganic phosphate. [35][36][37] The purpose of this study was to assess the physical compatibility of calcium chloride with NaGP in PN solutions intended for pediatric patients.…”

Avoidance of Overt Precipitation and Patient Harm Following Errant Y‐Site Administration of Calcium Chloride and Parenteral Nutrition Compounded With Sodium Glycerophosphate

“…The pharmacokinetic profiles of sodium phosphate and sodium glycerophosphate are nearly identical, and the products are both valid options as a phosphate source. 4 In terms of solubility in the presence of calcium, sodium glycerophosphate has been shown to be superior. PN solutions containing glycerophosphate are less likely to precipitate and allow for greater flexibility in calcium and phosphate dosing.…”