title: Glycerophosphate does not interact with components of parenteral nutrition.
abstract: OBJECTIVE
  The primary objective of this study was to determine and compare the pharmacokinetic (PK) profiles of inorganic phosphate in the serum after continuous administration of pure glycerophosphate and glycerophosphate contained in total parenteral nutrition (TPN) emulsions. This approach was selected to identify potential PK interactions between TPN components and glycerophosphate.
  
  
  METHODS
  The serum PK profile of inorganic phosphate after continuous intravenous administration of a sodium glycerophosphate containing TPN emulsion was determined in 10 healthy, white (5 male/5 female) volunteers. A pure sodium glycerophosphate formulation served as reference. Standard criteria of bioequivalence were applied. Subjects were enrolled in the double-blinded study and were randomly allocated to receive the test and reference preparations on two occasions in a 2-sequence crossover study design. The volunteers received 1/3 of the maximum recommended body weight- (BW) adjusted intravenous daily dosage (13.3 ml/kg BW) of the test drug over a period of 8 h. The amount of total phosphate (0.101 mmol/kg) and duration of administration were identical for the test and reference drugs. Study days were separated by washout periods of at least 88 h. Serum concentrations of total inorganic phosphate were measured serially over a 36-hour period using a validated method. A statistical mixed ANOVA, based on population averages, was used for testing bioequivalence between these study preparations.
  
  
  RESULTS
  The 90% confidence intervals (90% CIs) of inorganic phosphate in serum were calculated for the test/reference ratios of the area under the time-concentration curve from time 0 to 36 h (AUC₀₋₃₆), the maximum concentration (C(max)) and the concentration 5 min before the end of infusion (C(ss)) for a bioequivalence range from 0.80 to 1.25. The mean test/reference ratios fell completely within the 90% CIs with values of 1.016 (90% CI 1.005-1.028), 1.013 (90% CI 0.981-1.047) and 0.932 (90% CI 0.886-0.980) for AUC(0-36), C(max) and C(ss), respectively. In total, 3 mild adverse events in the reference group were detected after starting intravenous infusion, while no adverse events were observed in the test group after treatment.
  
  
  CONCLUSIONS
  Primary PK parameters were within the defined bioequivalence range of 0.8-1.25. Thus, inorganic phosphate levels were essentially similar between the two investigational medicinal products tested in the present study. These findings confirm the concept that nutritional components of the test drug do not significantly interact with glycerophosphate. The two study preparations proved to be safe during the investigation.
authors.affiliation: Fresenius Kabi Deutschland GmbH, Oberursel, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Topp
authors.forename: Olena
authors.initials: O
authors.lastname: Hochfeld
authors.forename: Staffan
authors.initials: S
authors.lastname: Bark
authors.forename: Matthias
authors.initials: M
authors.lastname: Grossmann
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
authors.forename: Harald
authors.initials: H
authors.lastname: Straatsma
authors.forename: Markus
authors.initials: M
authors.lastname: Rothenburger
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004339:Drug Compounding; D004347:Drug Interactions; D005260:Female; D005994:Glycerophosphates / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D010288:Parenteral Nutrition; D010289:Parenteral Nutrition, Total; D010710:Phosphates / Q000008:administration & dosage / Q000097:blood / Q000502:physiology / Q000652:urine; D010743:Phospholipids / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D013810:Therapeutic Equivalency; D013997:Time Factors; D055815:Young Adult
chemical_list: D005994:Glycerophosphates; D010710:Phosphates; D010743:Phospholipids