Gastric pH, Concentrations of Ranitidine in Gastric Juice and Plasma, and the Pharmacokinetics of Infused Ranitidine in Critically Ill Patients

The relationship between histamine H2-antagonist pharmacokinetic behaviour and the response of intragastric pH to physiological stress, and vital support measurements, have been prospectively evaluated in ten critically ill patients of mean (± s.d.) age 61 ± 16 years, mean weight 60 ± 9.7 kg, and APACHE (acute physiology and chronic health evaluation) II score 10 ± 6. In this double-blind, cross-over study patients received either a continuous ranitidine infusion made locally by Chimi-Darou, Iran (study drug) or Zantac (control drug). Subjects were randomized to receive 6.25 mg h−1 of the study drug for 24 h during the initial phase, after which drugs were switched for the next 24 h. The two phases of the study were separated by a wash-out period of 16 h. Intragastric pH was measured for 72 h with an antimony pH probe catheter. Concentrations of ranitidine in plasma and gastric juice were determined by HPLC. Mean ± s.e.m. gastric pH was 4.47 ± 0.65 for patients receiving the locally made study drug and 4.25 ± 0.69 for those receiving Zantac (P=0.5351). There was good correlation between intragastric pH and plasma ranitidine concentration (r=0.97, P=0.0055 and r=0.94, P=0.169 for study and control drugs, respectively). Ranitidine was also present in significant quantities in the gastric juice. There was no correlation between intragastric pH and gastric concentration of ranitidine (r=0.37, P=0.6142) for the control drug nor between the concentrations of the drug in the gastric juice and plasma (r=0.055, P=0.9292). There was no correlation between median pH and APACHE II score or Glasgow coma scale (GCS) score (P=0.557 and P=0.541, respectively).