Pharmacokinetics and Pharmacodynamics of Oral and Intravenous Cimetidine in Seriously III Patients

This study was done to determine if the pharmacokinetics and gastric pH response of intravenous cimetidine are superior to oral dosing in seriously ill patients. A paired study of intravenous followed by oral liquid cimetidine was given to eight men and two women who were inpatients in a VA Hospital. Treatment was prescribed for either upper gastrointestinal (GI) bleeding or prophylaxis against GI bleeding. All patients received cimetidine 300 mg every 6 hours intravenously on day 1 and orally on day 2. After the fourth dose each day, venous blood samples and gastric pH measurements were taken serially for 6 hours. Peak serum cimetidine concentration was 2.0 +/- 0.5 mg/L for the intravenous dose and 1.5 +/- 0.3 mg/L for the oral dose (P = .001). Area under the curve (AUC) of cimetidine concentration was 3.81 +/- 1.1 mg/hr/L for the intravenous dose and 4.19 +/- 1.22 mg/hr/L for the oral dose (P greater than .30). Bioavailability (AUCpo/AUCiv) was 1.13 +/- 0.25, demonstrating complete oral absorption. The time during a 6-hour dosing interval that the gastric pH remained above 3.0 was 3.3 +/- 2.1 hours for the intravenous dose and 2.5 +/- 2.3 hours for the oral dose, P = .171). The time that the serum cimetidine concentration remained above 0.5 mg/L was 2.0 +/- 0.9 hours for the intravenous dose and 2.7 +/- 1.0 hours for the oral dose (P = .055). We concluded that bioavailability, time that gastric pH is maintained greater 3.0, and time that the serum cimetidine concentration is greater than 0.5 mg/L for intravenous cimetidine are not significantly different from oral cimetidine in seriously ill patients.