1 The plasma pharmacokinetics of ranitidine (50 mg i.v.) have been studied in 17 critically ill patients in an intensive care unit. Measurements of gastric aspirate pH were also made in 16 of these patients. Ranitidine therapy was part of the patients' normal drug regimen. 2 Ranitidine plasma concentration was measured by high performance liquid chromatography and appropriate polyexponential equations were fitted to concentration-time data to enable calculation of relevant pharmacokinetic parameters. Values of the volume of the initial dilution space (median = 89 ml kg-') and volume of distribution at steady state (median = 1.541 kg-') were about 60% of corresponding mean literature values for healthy controls. Plasma clearance (median = 4.22 ml min7l kg-1) and terminal half-life (median = 4.7 h) were about 2-3 fold less and 2-3 fold greater, respectively, than values for healthy controls. There was wide interpatient variation in all the pharmacokinetic parameters. Renal impairment was considered to be largely responsible for the low plasma clearance. 3 Gastric aspirate pH was measured at 0, 1 and 7 h after ranitidine administration and 58% of samples were found to be above pH 4. Four patients had gastric pH values which were consistently below pH 4 despite average trough plasma ranitidine concentrations equal to or greater than those required for a 50% suppression of gastric acid secretion in normal volunteers.

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Cimetidine disposition was studied after rapid (1 min) intravenous infusion in eight critically ill patients aged between 20 years and 77 years; one patient was studied on two occasions. Cimetidine dose was 300 mg in seven patients and 400 mg in the remaining patient. Arterial plasma cimetidine concentrations at the end of the infusion were very high and ranged from approximately 15-35 mg/l. Pharmacokinetic parameters displayed wide interpatient variability (coefficients of variation of 30-50%) and significant relationships emerged between some of these parameters and certain patient characteristics. Most notable, total systemic plasma clearance of cimetidine was directly related to estimated creatinine clearance (p less than 0.01). This relationship might prove to be a useful method of individualizing cimetidine dosage in critically ill patients.

1. The bioavailability of two 5 mg tablet formulations of carbimazole (Neomercazole [A] and Carbazole [B]) have been compared in six euthyroid subjects. There was considerable inter-patient variation in absolute bioavailability although, for each subject, peak plasma concentrations of methimazole were similar with both formulations. 2. Mean peak plasma concentrations were seen on average 62 min after administration of tablet A as compared to 40 min after tablet B. This is consistent with the finding that the disintegration and dissolution times were shorter for formulation B than for formulation A. The mean area under the plasma concentration curve and the 6 h plasma concentration of methimazole tended to be greater after tablet A. These differences could be of significance in the treatment of thyrotoxicosis.