Journal of Bioequivalence & Bioavailability

Glycerophosphate does not interact with components of parenteral nutrition

2^nd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit-2011 and International Conference on Pharmaceutics & Novel Drug Delivery Systems

06-08 June 2011, Las Vegas, USA

Heinrich Topp, Olena Hochfeld, Staffan Bark, Matthias Grossmann, Christian Joukhadar, Martin Westphal, Harald Straatsma, Markus Rothenburger

Scientific Tracks Abstracts: JBB

Abstract:

T he primary objective of this study was to determine and compare the pharmacokinetic (PK) profi les of inorganic phosphate in the serum aft er continuous administration of pure glycerophosphate and glycerophosphate contained in total parenteral nutrition (TPN) emulsions. Th is approach was selected to identify potential PK interactions between TPN components and glycerophosphate. Th e serum PK profi le of inorganic phosphate aft er continuous intravenous administration of a sodium glycerophosphate containing TPN emulsion was determined in ten healthy, white (5 male/ 5 female) volunteers. A pure sodium glycerophosphate formulation served as reference (R). Standard criteria of bioequivalence were applied. Subjects were enrolled in the double-blinded study and were randomly allocated to receive the test (T) and R preparations on two occasions in a 2-sequence crossover study design. Th e volunteers received ⅓ of the maximum recommended body weight (BW) adjusted intravenous daily dosage (13.3 ml/kg BW) of the T drug over a period of 8 h. Th e amount of total phosphate (0.101 mmol/kg) and duration of administration were identical for the T and R drugs. Study days were separated by wash-out periods of at least 88 h. Serum concentrations of total inorganic phosphate were measured serially over a 36-h period using a validated method. A statistical mixed analysis of variance (ANOVA), based on population averages was used for testing bioequivalence between these study preparations. Th e 90% confi dence intervals (90% CIs) of inorganic phosphate in serum were calculated for the T/R ratios of the area under the time?concentration curve from time zero to 36 h (AUC 0-36 ), the maximum concentration (C max ) and the concentration 5 min before the end of infusion (C ss ) for a bioequivalence range from 0.80?1.25. Th e mean T/R ratios fell completely within the 90% CIs with values of 1.016 (CI: 1.005?1.028), 1.013 (CI: 0.981?1.047) and 0.932 (CI: 0.886?0.980) for AUC 0?36 , C max and C ss , respectively. In total, 3 mild adverse events in the R group were detected aft er starting intravenous infusion, while no adverse events were observed in the T group aft er treatment. Primary pharmacokinetic parameters were within the defi ned bioequivalence range of 0.8-1.25. Th us, inorganic phosphate levels were essentially similar between the two investigational medicinal products tested in the present study. Th ese fi ndings confi rm the concept that nutritional components of the T drug do not signifi cantly interact with glycerophosphate. Th e two study preparations proved to be safe during the investigation.