ABSTRACT
In a Latin square design, nine New Zealand white male rabbits (2.8-4.8 kg) each received intravenous indocyanine green (ICG) in doses of 2.5, 12.5, and 25 mg/kg. A period of 4 weeks separated consecutive experiments. A specific high-pressure liquid chromatographic (HPLC) assay and the traditional spectrophotometric (SPEC) method were used to monitor plasma ICG. The analyses demonstrated the ambiguous nature of the SPEC assay, and the HPLC procedure pointed to the presence of an unidentified ICG metabolite. Dose-dependent ICG disposition was evident from the ANOVA of the mean (+/- SD) clearances, namely, 17.09 (7.35), 4.50 (0.82), and 2.27 (0.57) mL X min-1 X kg-1 for the aforementioned doses, respectively. Analysis of variance of the clearances also demonstrated a significant ordering effect suggesting cumulative ICG toxicity. The mean ICG profiles for the three doses accorded with a novel three-compartment model containing two ICG distributional spaces in addition to a compartment (liver) responsible for ICG elimination from the circulation. A saturable uptake process into the eliminating compartment (Vmax = 0.93 mg X kg-1 X min-1; Km = 31.9 mg/L) accounted for the dose-dependent features. Additional studies in four unanesthetized rabbits with chronically catheterized bile ducts revealed no disparity between the SPEC and HPLC analyses of biliary ICG. The mean (+/- SD) ICG recovery in bile following an intravenous dose of about 12.5 mg/kg was 59.8 (16.3)%.
Subject(s)
Indocyanine Green/metabolism , Analysis of Variance , Animals , Bile/metabolism , Blood Proteins/metabolism , Chromatography, High Pressure Liquid , Kinetics , Male , Models, Biological , Protein Binding , Rabbits , SpectrophotometryABSTRACT
Extemporaneous dosage preparations for pediatrics are described including method of compounding, storage, stability and classification with respect to reliability of expiry date information. Information from the literature as well as our experience at The Hospital for Sick Children are discussed and presented in tabular format.
Subject(s)
Dosage Forms , Drug Compounding , Pediatrics , Child , Child, Preschool , Hospital Bed Capacity, 500 and over , Humans , OntarioABSTRACT
The development of a specific high-pressure liquid chromatographic (HPLC) assay, having a quantitative detection limit of 0.4 microgram/ml, is described for plasma indocyanine green. In a preliminary study, the HPLC method demonstrated that te traditional spectrophotometric procedure inaccurately quantitates the dye's degradation in aqueous medium since degradation products that absorb light at 770- nm are formed. In a further study, the spectrophotometric method yielded an erroneously low clearance of indocyanine green in the rabbit. In addition, the HPLC assay points to the possibility of metabolite formation of the dye in vivo.
