Lack of Effect of Histamine H₂‐Receptor Antagonists on Indocyanine Green Disposition Measured by Two Methods

Abstract: Eleven healthy male volunteers were treated according to a randomized, crossover design with ranitidine (300 mg/day), cimetidine (1200 mg/day), or nothing for 48 hours. Ninety minutes after the 48‐hour dose, each volunteer was given 0.5 mg/kg indocyanine green by iv bolus. Indocyanine green plasma concentrations were measured by the traditional spectrophotometric method at 800 nm and by HPLC simultaneously monitored at 214 and 656 nm. Neither histamine H₂‐receptor antagonist altered the disposition of indocyanine green. The mean (± S.D.) plasma clearance by the spectrophotometric method was 7.48 ± 2.07 (control), 7.15 ± 3.07 (ranitidine), and 6.88 ± 1.35 ml/min/kg (cimetidine). The power to detect a 20 per cent change is 0.87. The spectrophotometric method generally produced a biexponential plasma concentration decay, whereas the HPLC method resulted in a monoexponential decay. Analysis of the 5‐ to 15‐minute data by the conventional technique showed that although indocyanine green total plasma clearance was not significantly different for the two methods (P > 0.10), the volume of distribution was significantly greater (P < 0.001) and the elimination rate constant was significantly smaller (P < 0.001) for the spectrophotometric than the HPLC method. Although neither ranitidine nor cimetidine chronic administration alters indocyanine green disposition by either method, the absolute values of the pharmacokinetic parameters are dependent upon the analytical technique employed. 1984 American College of Clinical Pharmacology